SNPMiner Trials by Shray Alag


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Report for Mutation V30M

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 9 clinical trials

Clinical Trials


1 Safety and Efficacy of Orally Administered Fx-1006A in Patients With Familial Amyloid Polyneuropathy (FAP): A Randomized, Double-blind, Placebo-controlled Study

This study will examine whether Fx-1006A is effective in halting the progression of Familial Amyloid Polyneuropathy (FAP). Deposition of TTR amyloid is associated with a variety of human diseases. Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP. The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for amyloid diseases. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A, is hypothesized to stop progression of the disease in FAP patients. FAP is a uniformly fatal disease and Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience. This Phase 2/3 study will enroll early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of motor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months.

NCT00409175 Familial Amyloid Polyneuropathy Drug: Fx-1006A Drug: Placebo
MeSH:Polyneuropathies Amyloid Neuropathies Amyloid Neuropathies, Familial Amyloidosis
HPO:Amyloidosis Lattice corneal dystrophy Motor polyneuropathy Polyneuropathy

Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP. --- V30M ---

Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months. --- V30M ---

2. Documented V30M TTR mutation. --- V30M ---

Primary Outcomes

Description: Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than[<] 2) in NIS-LL score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment.

Measure: Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18

Time: Month 18

Description: Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.

Measure: Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18

Time: Baseline, Month 18

Secondary Outcomes

Description: NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) were scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS-LL score range 0-88, higher score=greater impairment.

Measure: Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to <2) in NIS-LL score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0 (normal) to 4 (paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment.

Measure: Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12

Time: Month 6, 12

Description: Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.

Measure: Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12

Time: Baseline, Month 6, 12

Description: Norfolk QOL-DN:35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7:scored as 1=symptom present, 0=symptom absent. Item 8-35: scored on 5-point Likert scale: 0=no problem, 4=severe problem (except item 32: -2=much better, 0=about same, 2=much worse). Norfolk QOL-DN summarized in 5 domains(score range):physical functioning/large fiber neuropathy(-2 to 58), activities of daily living(ADLs) (0 to 20), symptoms(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12); higher score=greater impairment, for each. Total score=-2 to138(higher score=worse QOL).

Measure: Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: Summated 7 score: composite score included five Nerve Conduction Studies (NCS) attributes (peroneal nerve distal motor latency, peroneal nerve compound muscle action potential, peroneal nerve motor conduction velocity, tibial nerve distal motor latency, and sural nerve sensory nerve action potential amplitude) along with Vibration Detection Threshold (VDT) obtained in great toes, and Heart Rate Response to Deep Breathing (HRDB) value. Score was determined through reference to normal values for age, sex and height. Total score range= -26 to 26, where higher score=worse nerve function.

Measure: Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: Summated 3 Nerve Tests Small Fiber Normal Deviates Score (NTSFnds) included cooling threshold for the lower limbs, heat pain threshold for the lower limbs and HRDB. Total score range= -11.2 to 11.2, where higher score=worse nerve function.

Measure: Change From Baseline in Summated 3 Score for Small Nerve Fiber Function at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: BMI was calculated by weight divided by height squared. mBMI was calculated by multiplying BMI by serum albumin levels to compensate for edema formation associated with malnutrition. A progressive decline in mBMI indicated worsening of disease severity.

Measure: Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, 12 and 18

Time: Baseline, Month 6, 12, 18

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.

Measure: Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer

Time: Week 8, Month 6, 12, 18

2 The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis

This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. Strong pre-clinical and clinical evidence support a daily dose of 20 mg of Fx-1006A to be the optimum dose to achieve stabilization of tetrameric TTR in ATTR-PN patients. Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. Safety and exploratory efficacy of Fx-1006A administered once daily for 12 months will also be evaluated in this patient population. This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. The study will be conducted in two parts. Part 1 will include a six-week dosing period during which all enrolled patients will receive oral Fx-1006A 20 mg soft gelatin capsules once daily for six weeks. At Week 6, blood samples will be collected from each patient to determine TTR stabilization. Patients who complete the Week 6 visit will continue receiving daily oral Fx-1006A 20 mg for up to a total of 12 months during Part 2 of this study. If it is determined that a patient is not stabilized at Week 6, the patient will be discontinued from the study. During Part 2, clinical outcomes will be measured at Months 6 and 12, based on NIS, Norfolk QOL-DN, mBMI, NCS, HRDB, SF-36, Karnofsky score, and echocardiography; NT-pro-BNP and troponin I levels will be measured at Baseline, Weeks 2 and 6, and Months 3, 6, and 12. Pharmacokinetic measurements will be made using samples collected at Baseline, Week 6, and Months 6 and 12. Safety and tolerability will be assessed throughout the study based on vital signs, physical examinations, ECG, echocardiography, 24-hour Holter monitoring, clinical laboratory tests (hematology, serum chemistry, and urinalysis), and monitoring adverse events and concomitant medication use. Day 1 will be defined as administration of the first dose of study drug. Clinic Visits will be conducted during Screening (Days -30 to -1) and at Baseline (Day 0), and Week 2, and Week 6, and Months 3, 6, and 12 (± 2 weeks of the scheduled date for post-Baseline visits). Monthly telephone contacts (+ 1 week of the scheduled date) will be made during months in which no investigative site visits are scheduled (Months 4, 5, 7, 8, 9, 10, and 11) for assessment of adverse events and concomitant medications. A final telephone contact to assess adverse events and concomitant medication usage will be made 30 days after the last dose of study drug. Patients who discontinue from the study at any time following enrollment will have a final visit performed, including all safety assessments, at the time of discontinuation. Any patient discontinuing after the Month 6 visit will also have all exploratory assessments performed.

NCT00630864 Transthyretin-associated Amyloidosis With Polyneuropathy Drug: Fx-1006A
MeSH:Polyneuropathies Amyloidosis
HPO:Amyloidosis Motor polyneuropathy Polyneuropathy

The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis. --- V30M ---

The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. --- V30M ---

The Effects of Fx-1006A on Transthyretin Stabilization and Clinical Outcome Measures in Patients With Non-V30M Transthyretin Amyloidosis This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. --- V30M --- --- V30M ---

Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. --- V30M ---

Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. --- V30M --- --- V30M ---

Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. --- V30M --- --- V30M --- --- V30M ---

Since disease presentation is similar between V30M and non-V30M TTR mutations associated with ATTR-PN and Fx-1006A has been shown to stabilize wild-type and V30M TTR in vitro and ex vivo, the present study is being conducted to determine the effects of Fx-1006A on TTR stabilization in ATTR-PN patients with TTR mutations other than V30M. --- V30M --- --- V30M --- --- V30M --- --- V30M ---

This is an open-label, multicenter, international study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with non-V30M TTR amyloidosis. --- V30M ---

- Patient has TTR-associated amyloidosis with V30M mutation. --- V30M ---

Primary Outcomes

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.

Measure: Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Week 6

Time: Week 6

Secondary Outcomes

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The FOI is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.

Measure: Percentage of Participants With Stabilized Transthyretin (TTR) Tetramer at Month 6 and 12

Time: Month 6, Month 12

Other Outcomes

Description: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Measure: Number of Participants With Treatment-Emergent Adverse Events (AEs)

Time: Baseline up to 30 days after the last dose

Description: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. On the basis of intensity, grade 3 was referred as severe, grade 4 as life-threatening and grade 5 as death.

Measure: Number of Participants With Greater Than or Equal to Grade 3 Treatment-Emergent Adverse Events

Time: Baseline up to 30 days after the last dose

Description: ECHO: investigator assessed test to assess cardiac function. ECHO abnormality criteria: any abnormality, valvular abnormality, pericardial effusion, abnormal regional wall motion, inferior vena cava respiratory variation, posterior (P) left ventricular (LV) wall/septal (S) thickness, right ventricular thickness, ejection fraction, ratio of early (E) diastolic transmitral flow and atrial(A) contraction velocity (E/A), ratio of 'E'to lateral/septal mitral annular velocity (e') (E/e'prime lateral, E/e'prime septal), E deceleration time (DT), isovolumic relaxation time (IVRT).

Measure: Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings

Time: Day 1 up to Month 12

Description: ECG: investigator assessed test to assess cardiac function. ECG abnormality criteria: any abnormality, arrhythmia, rhythm, conduction, morphology, myocardial infarction, ST segment, T waves and abnormal U waves.

Measure: Number of Participants With Clinically Significant Treatment-Emergent Electrocardiogram (ECG) Findings

Time: Day 1 up to Month 12

Description: Holter monitoring recorded heart rhythm. Holter monitoring abnormality criteria: any abnormality, atrial fibrillation/flutter, atrial tachycardia, non-sustained ventricular tachycardia (VT), sustained VT and sinus pause.

Measure: Number of Participants With Clinically Significant Treatment-Emergent Holter Monitoring Findings

Time: Day 1 up to Month 12

Measure: Number of Participants Who Discontinued Due to Clinical or Laboratory Adverse Events

Time: Baseline up to Month 12

Description: NIS assessed cranial nerves(nerve 3,6; facial, palate and tongue weakness),muscle weakness (respiratory; neck, elbow(E), wrist(W), finger(F), hip, knee(K) flexion; shoulder, thumb abduction; brachioradialis; E, W, hip, K extension; F spread; toe, dorsal and plantar ankle flexors; toe extensors); score: 0-4, higher score=more weakness, reflexes(biceps and triceps brachii; brachioradialis; quadriceps femoris; triceps surae), index F and great toe sensation(touch pressure, pin-prick, vibration, joint position)score:0=normal,1=decreased or 2=absent. Total score=0-244, higher score=more impairment.

Measure: Change From Baseline in the Neuropathy Impairment Score (NIS) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: NIS-LL: assessed muscle weakness, reflexes and sensation; scored separately for left and right limbs. Components of muscle weakness (hip and knee flexion, hip and knee extension, ankle dorsiflexors, ankle plantar flexors, toe extensors, toe flexors) are scored on 0 to 4 scale, higher score=greater weakness. Components of reflexes (quadriceps femoris, triceps surae) and sensation (touch pressure, pin-prick, vibration, joint position) were scored 0 = normal, 1= decreased, or 2 = absent. Total possible NIS-LL score range 0-88, higher score=greater impairment.

Measure: Change From Baseline in the Neuropathy Impairment Score-Lower Limb (NIS-LL) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than [<] 2) in Neuropathy Impairment Score- Lower Limb (NIS-LL) score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment.

Measure: Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6, Month 12

Time: Month 6, Month 12

Description: TQOL= sum of all Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) items,a 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on QOL of participants with DN; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). Total TQOL score=-2 to 138;higher score=worse quality of life.

Measure: Change From Baseline in Total Quality of Life (TQOL) Score at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Norfolk QOL-DN:35-item participant-rated questionnaire to assess impact of DN on QOL; Item 1-7: scored as 1=symptom present, 0=symptom absent. Item 8-35: scored on 5-point Likert scale:0=no problem, 4=severe problem(except item 32: -2=much better, 0=about same, 2=much worse).Norfolk QOL-DN summarized in 5 domains (score range): physical functioning/large fiber neuropathy(-2 to 58), activities of daily living(ADLs) (0 to 20), symptom(0 to 32), small fiber neuropathy(0 to 16), autonomic neuropathy(0 to 12);higher score=greater impairment, for each. Total score=-2 to 138 (higher score=worse QOL).

Measure: Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: NCS: quantitative measures of peripheral nerve dysfunction consists of 5 attributes: peroneal nerve (PN) motor distal latency, PN compound muscle action potential, PN motor conduction velocity, tibial nerve distal motor latency, sural nerve sensory nerve action potential. Normal deviates (Z-score) summated into composite score (higher score=worsened nerve fiber function). Z-score is the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean.

Measure: Change From Baseline in Nerve Conduction Studies (NCS) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: HRDB test was used to evaluate the cardio-vagal response. Participant took a series of 8 deep breaths and average heart rate difference was measured and compared to normative data. The main factor affecting HRDB is age, with older patients showing less heart rate variability. R-R (time between two consecutive R waves in the electrocardiogram) response to deep breathing was reported as the normal deviates (Z-score), the defined position of the result in normal probability distribution with a mean of 0 and standard deviation (std) of 1 and describes how far a score is (in std) from the mean.

Measure: Change From Baseline in Heart Rate Response to Deep Breathing (HRDB) at Month 6 and Month 12

Time: Baseline, Month 6, Month 12

Description: BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m^2). mBMI was calculated by multiplying BMI by serum albumin levels [gram/liter (g/L)]. mBMI was measured as kg/m^2*g/L. A progressive decline in mBMI indicated worsening of disease severity.

Measure: Change From Baseline in Modified Body Mass Index (mBMI) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health and two total scores (physical component summary [PCS] and mental component summary [MCS]. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

Measure: Change From Baseline in Overall Quality of Life and Individual Domains of the Short-form-36 (SF-36) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Echocardiography was used to measure interventricular septal thickness (IVST), posterior left ventricular wall thickness (PLVWT), right ventricular wall thickness (RVWT), left atrial diameter (LAD): anterior-posterior (ant-post), medio-lateral, superior-inferior (sup-inf) and left ventricular end diastolic diameter (LVED), relative LV wall thickness (RLVWT).

Measure: Change From Baseline in Echocardiography (ECHO) Parameters at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Left atrial volume was measured by echocardiography.

Measure: Change From Baseline in Left Atrial Volume at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Cardiac MRI was done to measure left ventricular (LV) end systolic volume, left ventricle (LV) stroke volume.

Measure: Change From Baseline in Left Ventricular (LV) End Systolic Volume, Left Ventricle (LV) Stroke Volume at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Fractional shortening (FS) is the fraction of any diastolic dimension that is lost in systole. Percent of FS was calculated as difference between end-diastolic dimension (EDD) and end-systolic dimension (EDS) divided by EDD.

Measure: Change From Baseline in Fractional Shortening at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Cardiac MRI was done to measure left ventricular ejection fraction (LVEF) which was the fraction of the end-diastolic volume (EDV) that was ejected out of left ventricle with each contraction.

Measure: Change From Baseline in Left Ventricular (LV) Ejection Fraction at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. Increased LVM was associated with cardiovascular morbidity and mortality.

Measure: Change From Baseline in Left Ventricular Mass (LVM) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. IVRT is the time between the closure of the aortic valve and the opening of the mitral valve. Mitral deceleration time (MDT) was the time taken from the maximum E point wave to baseline. E wave arises due to early diastolic filling.

Measure: Change From Baseline in Isovolumetric Relaxation Time (IVRT), Mitral Deceleration Time at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: The diameter at the base of the aortic root, the basal ring, is also called the aortic annulus diameter.

Measure: Change From Baseline in Aortic Annulus Diameter at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Tricuspid peak velocity was measured by echocardiography.

Measure: Change From Baseline in Tricuspid Peak Velocity at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Systolic right ventricular pressure can be estimated on echocardiography by adding right atrial pressure (RAP) to the trans-tricuspid gradient derived from the tricuspid regurgitation velocity.

Measure: Change From Baseline in Tricuspid Pulmonary Artery Systolic Pressure (PASP) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Doppler principle was used to measure the mitral peak early (E) diastolic transmitral flow, mitral peak atrial (A) contraction velocity and annular velocities at the lateral and septal areas of the mitral annulus. s': systolic velocity during ejection, e': early diastolic mitral annular velocity, a': late diastolic mitral annular velocity.

Measure: Change From Baseline in Doppler Data at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Ratio of early (E) diastolic transmitral flow velocity and atrial (A) contraction velocity (E/A) and ratio of the early (E) diastolic transmitral flow velocity to the mitral annular velocity (e') (E/e') were estimated.

Measure: Change From Baseline in e:e' Lateral Ratio , Ratio of Peak Mitral Early Diastolic and Atrial Contraction Velocity (E/A Ratio) at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: LV mass was calculated from the product of the myocardial volume and specific gravity of heart muscle, estimated by echocardiography. QRS score (the sum of QRS voltages in the peripheral leads) was used as an index of "electrical" LV mass.

Measure: Change From Baseline in Left Ventricular (LV) Mass/Voltage Ratio at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: LA volume index (LAVI), was the value of LA volume divided by body surface area, to measure LA size.

Measure: Change From Baseline in Left Atrial (LA) Volume Index at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: NT-proBNP was a cardiac marker which had the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage.

Measure: Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) at Week 2, Week 6, Month 3, Month 6, Month 12

Time: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12

Description: Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (no evidence of disease). Higher score means higher ability to perform daily tasks.

Measure: Change From Baseline in Karnofsky Performance Status Scale at Month 6, Month 12

Time: Baseline, Month 6, Month 12

Description: Troponin I is a cardiac injury biomarker. Higher concentrations of this marker in blood are associated with heart injury.

Measure: Change From Baseline in Troponin I Levels at Week 2, Week 6 , Month 3, Month 6, Month 12

Time: Baseline, Week 2, Week 6 , Month 3, Month 6, Month 12

3 OPEN-LABEL SAFETY AND EFFICACY EVALUATION OF FX-1006A IN SUBJECTS WITH TRANSTHYRETIN (TTR) AMYLOIDOSIS

This is a Phase 3, open-label study designed to obtain additional long-term safety and efficacy data for oral tafamidis (20 mg soft gelatin capsule) administered once daily (QD). In addition, this study continued to provide tafamidis to Val30Met subjects who had completed Protocol Fx-006 (a 1-year, open-label extension study to Protocol Fx-005 which was a randomized, double-blind, placebo-controlled, 18-month study to evaluate the safety and efficacy of tafamidis) or non-Val30Met subjects who had completed Protocol Fx1A-201 (a Phase 2, open-label study to evaluate TTR stabilization, safety, and tolerability of tafamidis) for up to 10 years or until subjects had access to tafamidis for ATTR-PN via prescription. Upon regulatory approval for the treatment of ATTR-PN in their respective country and access to prescription tafamidis, subjects may have been withdrawn from the study. Such subjects were considered study completers.

NCT00925002 ATTR-PN Drug: Tafamidis
MeSH:Amyloidosis
HPO:Amyloidosis

In addition, this study continued to provide tafamidis to Val30Met subjects who had completed Protocol Fx-006 (a 1-year, open-label extension study to Protocol Fx-005 which was a randomized, double-blind, placebo-controlled, 18-month study to evaluate the safety and efficacy of tafamidis) or non-Val30Met subjects who had completed Protocol Fx1A-201 (a Phase 2, open-label study to evaluate TTR stabilization, safety, and tolerability of tafamidis) for up to 10 years or until subjects had access to tafamidis for ATTR-PN via prescription. --- Val30Met ---

In addition, this study continued to provide tafamidis to Val30Met subjects who had completed Protocol Fx-006 (a 1-year, open-label extension study to Protocol Fx-005 which was a randomized, double-blind, placebo-controlled, 18-month study to evaluate the safety and efficacy of tafamidis) or non-Val30Met subjects who had completed Protocol Fx1A-201 (a Phase 2, open-label study to evaluate TTR stabilization, safety, and tolerability of tafamidis) for up to 10 years or until subjects had access to tafamidis for ATTR-PN via prescription. --- Val30Met --- --- Val30Met ---

Primary Outcomes

Measure: Percentage of patients with a change from baseline in Neuropathy Impairment Score (NIS)

Time: Baseline up to 10 years

Measure: Percentage of patients with a change from baseline in Total Quality of Life (TQOL) score

Time: Baseline up to 10 years

Measure: Number or Percentage of patients with a change from baseline in Karnofsky Performance Scale Index

Time: Baseline up to 10 years

Measure: Percentage of patients with a change in subject ambulation as measured by modified Polyneuropathy Disability (mPND) score

Time: Baseline up to 10 years

Secondary Outcomes

Measure: Incidence of treatment emergent adverse events from baseline through 10 years

Time: Baseline up to 10 years

Measure: Number or percentage of patients with change from baseline in Clinical Laboratory parameters

Time: Baseline up to 10 years

Measure: Number of patients with change in ECG parameters

Time: Baseline up to 10 years

Measure: Number or percentage of patients with change from baseline in Vital sign measurements

Time: Baseline up to 10 years

Measure: Descriptive summary of physical examination findings for patients through 10 years

Time: Baseline up to 10 years

Measure: Descriptive summary of concomitant medication use for patients through 10 years

Time: Baseline up to 10 years

4 The Effect On Transthyretin Stabilization, Safety, Tolerablity, Efficacy And Pharmacokinetics Of Orally Administered Tafamidis In Transthyretin Amyloid Polyneuropathy Patients With V30m Or Non-v30m Transthyretin: A Phase Iii, Open-label Study

Tafamidis has been developed as an oral specific stabilizer of transthyretin tetramer.

NCT01435655 Transthyretin Familial Amyloid Polyneuropathy Drug: tafamidis
MeSH:Polyneuropathies Amyloid Neuropathies Amyloid Neuropathies, Familial Amyloidosis
HPO:Amyloidosis Lattice corneal dystrophy Motor polyneuropathy Polyneuropathy

The Effect Of Tafamidis For The Transthyretin Amyloid Polyneuropathy Patients With V30M Or Non-V30M Transthyretin Tafamidis has been developed as an oral specific stabilizer of transthyretin tetramer. --- V30M ---

The Effect Of Tafamidis For The Transthyretin Amyloid Polyneuropathy Patients With V30M Or Non-V30M Transthyretin Tafamidis has been developed as an oral specific stabilizer of transthyretin tetramer. --- V30M --- --- V30M ---

Inclusion Criteria: - Transthyretin amyloid polyneuropathy with V30M or non-V30M transthyretin mutation. --- V30M ---

Inclusion Criteria: - Transthyretin amyloid polyneuropathy with V30M or non-V30M transthyretin mutation. --- V30M --- --- V30M ---

Primary Outcomes

Description: TTR tetramer level for each plasma sample was assessed using a validated immunoturbidimetric assay before and after urea denaturation. The Fraction of Initial (FOI) tetramer concentration is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer average concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI. A patient who has the "TTR stabilization" is defined as the patient whose percent stabilization is equal to or more than 32%.

Measure: Number of Participants With Transthyretin (TTR) Stabilization at Week 8 Compared With Baseline as Measured by a Validated Immunoturbidimetric Assay

Time: 8 weeks

Secondary Outcomes

Description: The NIS provides a total body single score of neuropathic deficits (score range: 0-122, higher score = more deficit), comprising subset scores for cranial nerves, muscle weakness, reflexes, and sensation (based on mean of 2 scores in 1 week period; each item scored separately for left and right). The NIS-LL is a subscale that provides a score for the lower limbs functions (muscle weakness, reflexes and sensation in great toe) and has a score range of 0-44 (higher score = more deficit). The NIS-UL is a subscale that provides a score for the upper body functions (muscle weakness [including cranial nerves], reflexes and sensation in finger) and has a score range of 0-78 (higher score = more deficit). The components for cranial nerves and muscle weakness are scored from 0 (Normal) to 4 (Paralysis), and those for reflexes and sensation from 0 (Normal) to 2 (Absent). For all items, higher scores indicate greater impairment.

Measure: Change From Baseline in Neuropathy Impairment Score (NIS); NIS (Total), NIS-LL (Lower Limb) and NIS-UL (Upper Limb) at Week 26, Week 52 and Week 78

Time: Baseline, Week 26, Week 52, Week 78

Description: Norfolk QOL-DN is a 35-item participant-rated questionnaire. It consists of 5 domains: Physical Functioning/Large Fiber [score range: -4 - 56] , Activities of Daily Living (ADL) [0 - 20], Symptoms [0 - 32], Small Fiber [0 - 16] and Autonomic [0 - 12]. Total of quality of life (TQOL) score is the sum of all five domains with a range of -4 to 136 (Pfizer Data Standards). Higher scores on each item of the Norfolk QOL-DN TQOL indicate worse quality of life.

Measure: Change From Baseline in Scores of the Total Quality of Life (TQOL) and 5 Domains as Measured by the Norfolk QOL - Diabetic Neuropathy (Norfolk QOL-DN) at Week 26, Week 52 and Week 78.

Time: Baseline, Week 26, Week 52, Week 78

Description: The Σ7 NTs nds measures primarily large-fiber function. It is a composite score derived from five NCS attributes (peroneal nerve distal motor latency, peroneal nerve compound muscle action potential, peroneal nerve motor conduction velocity, tibial nerve distal motor latency, and sural nerve sensory nerve action potential amplitude) along with VDT obtained in great toes by Quantitative Sensory Testing (QST), and HRDB value. It is defined as 7 times the mean of non-missing values of, the five normal deviates of NCS, HRDB, and average normal deviate for VDT of toes. Score was determined through reference to normal values for age, sex, height and abnormalities scored. Total score range is approximately -26 to 26, where higher score=worse nerve function.

Measure: Change From Baseline in Summated 7 Nerve Tests Normal Deviate Score (∑ 7 NTs Nds) as Measured by Nerve Conduction Studies (NCS), Vibration Detection Threshold (VDT) and Heart Rate Response to Deep Breathing (HRDB) at Week 26, Week 52, and Week 78

Time: Baseline, Week 26, Week 52, Week 78

Description: The Σ3 NTSF nds measures small-fiber function. It is a composite score defined as 3 times the mean of non-missing values of normal deviates of cooling threshold for lower limbs, heat pain intermediate response for lower limbs, and HRDB. The total score range is approximately -11.2 to 11.2, with a higher score demonstrating worse nerve function.

Measure: Change From Baseline in Summated 3 Nerve Tests Small Fiber Normal Deviate Score (∑ 3 NTSF Nds) as Measured by Cooling and Heat Pain Thresholds by QST and HRDB at Week 26, Week 52 and Week 78

Time: Baseline, Week 26, Week 52, Week 78

Description: The mBMI was calculated by multiplying the BMI (the weight in kilograms divided by the square of the height in meters) by serum albumin level (gram/liter). Change in mBMI was calculated as the mBMI at the given week minus the Baseline mBMI.

Measure: Change From Baseline in Modified Body Mass Index (mBMI) at Week 8, Week 26, Week 52 and End of Study

Time: Baseline, Week 8, Week 26, Week 52, End of Study

Description: Ambulatory status was evaluated using walking ability scale in polyneuropathy disability score. The ambulatory status was evaluated as: 0=Good, 1=Sensory disturbances in the feet but able to walk without difficulty, 2=Some difficulties with walking but can walk without aid, 3a=Able to walk with 1 stick or crutch, 3b=Able to walk with 2 sticks or crutches, 4=Not ambulatory, confined to a wheelchair or bedridden.

Measure: Change From Baseline in Ambulatory Status at Week 26, Week 52 and Week 78

Time: Baseline, Week 26, Week 52, Week 78

Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The TTR tetramer level for each plasma sample was measured before and after urea denaturation. The Fraction of Initial (FOI) tetramer concentration is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI. A patient who has the "TTR stabilization" is defined as the patient whose percent stabilization is equal to or more than 32%.

Measure: Number of Participants With Transthyretin (TTR) Stabilization at Week 26, Week 52, and Week 78 Compared With Baseline as Measured by a Validated Immunoturbidimetric Assay

Time: Baseline, Week 26, Week 52, Week 78

Other Outcomes

Description: Mean plasma concentration of tafamidis at 3 hours after administration

Measure: Plasma Concentration of Tafamidis at Week 8, Week 26, Week 52 and Week 78

Time: Week 8, Week 26, Week 52, Week 78

5 Cross-sectional, Non-interventional Burden Of Disease (Bod) Study In Patients With Transthyretin Familial Amyloidosis Polyneuropathy (Ttr-fap) Or Transthyretin Cardiomyopathy (ttr-cm) And Caregivers

This study is an online (web-based) or paper-based survey for patients with transthyretin familial amyloidosis polyneuropathy (TTR-FAP) and caregivers. The results will be used to describe the emotional, physical, and financial impact of having TTR-FAP or caring for someone who has the disease.

NCT01604122 Transthyretin Familial Amyloidosis Polyneuropathy (TTR-FAP) Transthyretin Cardiomyopathy (TTR-CM) Familial Amyloid Cardiomyopathy Senile Systemic Amyloidosis (SSA) Other: No drug Other: No drug
MeSH:Polyneuropathies Amyloid Neuropathies Cardiomyopathies Amyloidosis, Familial Amyloidosis
HPO:Amyloidosis Cardiomyopathy Motor polyneuropathy Polyneuropathy

In this outcome, number of participants with each type of resulted mutation type (Val30Met, wild type TTR, Phe64Leu, Ser77Tyr, Thr60Ala or other than these) were reported. --- Val30Met ---

Primary Outcomes

Description: Main characteristics included were education level and employment status which were asked from all participants and caregivers. Type of job (full-time, part-time) was asked only from those participants and caregivers who provided their employment status as employed. Those who were unemployed reported their cause of unemployment, whether it was due to ATTR or not.

Measure: Demographical Characteristics of Participants

Time: Baseline (Day 1)

Description: Duration of disease was defined as the time from diagnosis of disease until baseline visit. This outcome measure was planned to be assessed for reporting arm of participants diagnosed with ATTR.

Measure: Disease Characteristics of Participants: Disease Duration

Time: Baseline (Day 1)

Description: Genetic mutation leads to misfolding of protein transthyretin (TTR) which results in ATTR. In this outcome, number of participants with each type of resulted mutation type (Val30Met, wild type TTR, Phe64Leu, Ser77Tyr, Thr60Ala or other than these) were reported. This outcome was planned to be assessed for reporting arm of participants diagnosed with ATTR.

Measure: Disease Characteristics of Participants: Mutation Type

Time: Baseline (Day 1)

Description: TTR protein is primarily synthesized in the liver. Liver transplantation was considered as one of the measure to eliminate the main source of variant TTR. In the study, participants who were diagnosed with ATTR were asked for their liver transplantation status (whether they had transplantation or not). In this outcome measure, number of participants with liver transplant status were reported. This outcome was planned to be assessed for reporting arm of participants diagnosed with ATTR.

Measure: Disease Characteristics of Participants: Liver Transplantation Status

Time: Baseline (Day 1)

Description: Family history of participants diagnosed with ATTR was assessed to determine whether family history of ATTR was a significant risk factor for ATTR or not. This outcome was planned to be assessed for reporting arm of participants diagnosed with ATTR.

Measure: Disease Characteristics of Participants: Number of Participants With Family History of ATTR

Time: Baseline (Day 1)

Description: Mobility, i.e., ability to walk was assessed as a part of loss of functioning in the participants diagnosed with ATTR. In this outcome, number of participants with their different mobility status along with the use of mobility aids (able to walk normally, some problems with feet but able to walk without difficulty, some difficulty walking but can walk without help, confined to bed all the time, need 1 cane or crutch to walk, need 2 canes/crutches or a walker to walk) were reported.

Measure: Disease Characteristics of Participants: Mobility Status

Time: Baseline (Day 1)

Description: SF-12 was a patient reported outcome survey that represented overall health status by measuring 8 health-related aspects of an individual: Body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Responses on the SF-12 were also used to calculate 2 summary scores: Physical component score (PCS) and mental component score (MCS). The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health), where 100 indicated good health condition.

Measure: 12-Item Short-Form Health Survey (SF-12) Scores

Time: Baseline (Day 1)

Description: HADS: participant rated 14-item questionnaire with 2 subscales; HADS-anxiety scale (HADS-A) and HADS-depression scale (HADS-D). HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items and the participant responds as to how each item applies to him/her over the past week prior to baseline visit, on 4-point response scale. Separate scores were calculated for anxiety and depression with score ranges from 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score range was from 0 to 21 for each subscale; higher score indicating greater severity of anxiety and depression symptoms.

Measure: Hospital Anxiety and Depression Scale (HADS): Depression and Anxiety Subscale Scores

Time: Baseline (Day 1)

Description: EQ-5D-3L: participant rated questionnaire to assess generic health status in two parts: single utility score and visual analog scale. For utility score, participants rated their current health state on 5 dimensions: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression with each dimension having three levels of function: 1 indicates no problem; 2 indicates some problem; 3 indicates extreme problem. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score was transformed and results in a total score range of 0.05 to 1.00; higher scores indicating a better health state.

Measure: Euro Quality of Life (EQ-5D-3L)- Health State Profile Utility Score

Time: Baseline (Day 1)

Description: EQ-5D: participant rated questionnaire to assess generic health status in two parts: single utility score and visual analog scale. The VAS component rated the current health state on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicating a better health state.

Measure: Euro Quality of Life (EQ-5D-3L)- Visual Analog Scale (VAS) Score

Time: Baseline (Day 1)

Description: The WPAI assesses work productivity and impairment. It was a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days prior to baseline visit. The questionnaire asked about current employment status, hours worked, hours missed from work and degree to which a specified health problem (ATTR) or caregiving affected work productivity and regular activities. Percentage of work time missed of participants were recorded and reported.

Measure: Work Productivity and Activity Impairment- Specific Health Version (WPAI-SH): Percent of Work Time Missed

Time: Baseline (Day 1)

Description: The WPAI assesses work productivity and impairment. It was a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days prior to baseline visit. The questionnaire asks about current employment status, hours worked, hours missed from work and degree to which a specified health problem (ATTR) or caregiving affected work productivity and regular activities. Component scores included percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. The computed percentage range for each sub-scale was from 0-100, where higher numbers indicating greater impairment and less productivity.

Measure: Work Productivity and Activity Impairment- Specific Health Version: Percent Impairment While Working

Time: Baseline (Day 1)

Description: The WPAI assesses work productivity and impairment. It was a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days prior to baseline visit. The questionnaire asked about current employment status, hours worked, hours missed from work and degree to which a specified health problem (ATTR) or caregiving affected work productivity and regular activities. Component scores included percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. The computed percentage range for each sub-scale was from 0-100, where higher numbers indicating greater impairment and less productivity.

Measure: Work Productivity and Activity Impairment- Specific Health Version: Percent Overall Work Impairment

Time: Baseline (Day 1)

Description: The WPAI assesses work productivity and impairment. It was a 6-item questionnaire used to assess the degree to which a specified health problem affected work productivity and regular activities over the past 7 days prior to baseline visit. The questionnaire asks about current employment status, hours worked, hours missed from work and degree to which a specified health problem (ATTR) or caregiving affected work productivity and regular activities. Component scores included percent work time missed due to the health problem; percent impairment while working due to problem; percent overall work impairment due to problem; and percent activity impairment due to problem. The computed percentage range for each sub-scale was from 0-100, where higher numbers indicating greater impairment and less productivity.

Measure: Work Productivity and Activity Impairment- Specific Health Version: Percent Activity Impairment

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR and caregivers was assessed by questions concerning a variety of different types of treatment and resources including outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs (for example, costs of travel to receive care).

Measure: Healthcare Resource Use Survey: Number of Outpatient Visits to Healthcare Providers

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR and caregivers was assessed by questions concerning a variety of different types of treatment and resources including outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs (for example, costs of travel to receive care).

Measure: Healthcare Resource Use Survey: Number of Hospitalizations

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR and caregivers was assessed by questions concerning a variety of different types of treatment and resources including outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs (for example, costs of travel to receive care).

Measure: Healthcare Resource Use Survey: Number of Emergency Care Visits

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR was assessed by questions concerning a variety of treatments and resources included outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs. Number of participants (diagnosed with ATTR) who visited non-medical practitioners (nutrition consultant/dietician, chiropractor, acupuncturist, massage therapist, occupational therapist or other than these) for symptomatic treatments were reported.

Measure: Healthcare and Resource Use Survey: Symptomatic Treatment of Participants

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR was assessed by questions concerning a variety of treatments and resources included outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs. Number of visits of participants (diagnosed with ATTR) who visited non-medical practitioners (nutrition consultant/dietician, chiropractor, acupuncturist, massage therapist, occupational therapist or other than these) for symptomatic treatments were reported.

Measure: Healthcare Resource Use Survey: Number of Symptomatic Treatment Visits

Time: Baseline (Day 1)

Description: Healthcare resources use survey of participants diagnosed with ATTR was assessed by questions concerning a variety of treatments and resources included outpatient visits to healthcare providers, hospitalizations, emergency/urgent care visits, symptomatic treatments, and out-of-pocket costs (expenditure on nutritional supplements, non-prescription medications and travel to receive medical care).

Measure: Healthcare Resource Use Survey: Out-of-Pocket Costs

Time: Baseline (Day 1)

Description: Participants diagnosed with ATTR rated their pain due to the health condition based on 3 items: pain right now, average pain in the past week, and worst pain in the past week prior to baseline visit. All 3 items were rated on an 11-point numeric rating scale ranging from 0=none to 10=severe pain, where higher scores indicated severe pain.

Measure: Participants Pain Score

Time: Baseline (Day 1)

Description: Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of neuropathy on the quality of life of participants diagnosed with ATTR. Scoring was based on 35 questions that yield a TQOL as well as 5 subscale scores: activities of daily living, large fiber neuropathy/physical functioning, small fiber neuropathy, autonomic neuropathy, and symptoms. TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life. This outcome measure was planned to be analyzed only for the reporting arm of participants diagnosed with ATTR.

Measure: Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) Total Quality of Life (TQOL): Total Scores

Time: Baseline (Day 1)

Description: Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of neuropathy on the quality of life of participants diagnosed with ATTR. It was summarized in 5 domains: (1) Activities of daily living (score ranges from 0 to 20, where higher score=worse quality of life); (2) Large fiber neuropathy/physical functioning (score ranges from -2 to 58, where higher score=worse condition); (3) Small fiber neuropathy (score ranges from 0 to 16, where higher score=worse condition); (4) Autonomic neuropathy (score ranges from 0 to 12, where higher score=worse condition) and (5) Symptoms (score ranges from 0 to 32, where higher score=less symptoms of disease). Total possible score range= -2 to 138, where higher score=worse quality of life. This outcome measure was analyzed only for the participants diagnosed with ATTR.

Measure: Norfolk Quality of Life-Diabetic Neuropathy Total Quality of Life: Subscale Scores

Time: Baseline (Day 1)

Description: KCCQ was a 23-item participant-completed questionnaire that assessed health status and health-related quality of life (HRQoL) in participants with heart failure. It was quantified in to following 10 summary scores: physical limitation, symptom frequency, symptom severity, and symptom stability, total symptoms, quality of life, social interference, self-efficacy, overall summary and clinical summary. Each summary score was scaled to range from 0 (minimum) to 100 (maximum), with higher scores representing greater disability. Total score ranged from 0 to 100, where higher scores indicated better functioning, fewer symptoms, and better disease specific quality of life.

Measure: Kansas City Cardiomyopathy Questionnaire (KCCQ) Scores

Time: Baseline (Day 1)

Description: ZBI was a 22-item questionnaire designed to evaluate five broad aspects of caregiver burden in terms of personal and role strain associated with caregiving. Five broad aspects were: burden in the relationship, emotional well-being, social and family life, finances, loss of control over one's life. Each item rated on a 5 point scale anchored at 0 for "never" and 4 for "nearly always." Total score ranges from 0-88 with higher scores indicating increased burden of care.

Measure: Zarit Burden Interview (ZBI): Total Scores

Time: Baseline (Day 1)

Description: A questionnaire designed to evaluate aspects of caregiver burden in terms of personal and role strain associated with caregiving. Total score of ZBI scale ranges from 0-88 with higher scores indicating increased burden of care. Five subscale scores were also calculated: (1) Burden in the relationship (consist of 6-items, ranging from 0 to 24 where higher scores indicating increased burden in relationship); (2) Emotional well-being (consisting of 7-items, ranging from 0 to 28 where higher scores indicating worse condition; (3) Social and family life (consisting of 4-items, ranging from 0 to 16 where higher scores indicating worse life condition); (4) Finances (consisting of a single item, scored from 0 to 4 where higher scores indicating worse financial condition); and (5) Loss of control over one's life (consisting of 4-items, ranging from 0 to 16 where higher scores indicating worse control over life).

Measure: Zarit Burden Interview: Subscale Scores

Time: Baseline (Day 1)

Description: Caregivers completed a series of questions related to the number of hours per week spent on providing care and support to the participants diagnosed with ATTR.

Measure: Caregiver Burden Items Assessment: Number of Hours Per Week Spent in Care of the Participants With ATTR

Time: Baseline (Day 1)

Description: Caregivers completed a series of questions related to the loss in their working time while providing care and support to the participants diagnosed with ATTR.

Measure: Caregiver Burden Items Assessment: Work Time Lost

Time: Baseline (Day 1)

Description: Caregivers completed a series of questions related to the total cost spent on providing healthcare support to participants diagnosed with ATTR.

Measure: Caregiver Burden Items Assessment: Total Cost

Time: Baseline (Day 1)

6 Screening for the Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP): An International, Multicenter, Epidemiological Protocol

An International, multicenter, epidemiological observational study investigating the prevalence of Transthyretin-Related Familial Amyloidotic Polyneuropathy (TTR-FAP) in participants with small fiber polyneuropathy of no obvious etiology.

NCT01705626 Polyneuropathy, Amyloid Neuropathic Pain Cardiac Failure Orthostatic Hypotension Gastrointestinal Disorders
MeSH:Gastrointestinal Diseases Neuralgia Polyneuropathies Hypotension, Orthostatic Amyloid Neuropathies Hypotension Heart Failure Digestive System Diseases
HPO:Abnormality of the gastrointestinal tract Congestive heart failure Hypotension Left ventricular dysfunction Motor polyneuropathy Orthostatic hypotension Polyneuropathy Right ventricular failure

It accounts several thousand cases worldwide, with Val30Met mutation identified in most patients and with endemic foci in Portugal, Sweden and Japan. --- Val30Met ---

Primary Outcomes

Description: Dry Blood Spot (DBS) samples will be genetically validated via combination of Next-Generation Sequencing (the mutation will be confirmed by Sanger sequencing) and the Multiplex ligation-dependent probe amplification (MLPA) of TTR gene

Measure: Epidemiological analysis of prevalence of the TTR FAP in participants with small fiber polyneuropathy of no obvious etiology.

Time: 3 years

Secondary Outcomes

Description: Samples carrying a mutation in the TTR gene will be biochemically analyzed via liquid chromatography multiple reaction monitoring MS and compared with a merged control cohort, in order to establish TTR mutation-specific biomarker/s.

Measure: Establishment of a biomarker in TTR-positive cohort

Time: 3 years

7 Biomarker for Transthyretin-Related Familial Amyloidotic Polyneuropathy - An International, Multicenter, Epidemiological Protocol

International, multicenter, observational, longitudinal study to identify biomarker/s for the development of a new MS-based biomarker for the early and sensitive diagnosis of Transthyretin-Related Familial Amyloidotic Polyneuropathy from blood and number of correctly identified patients with Transthyretin-Related Familial Amyloidotic Polyneuropathy

NCT02713880 Transthyretin Amyloidosis Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy Transthyretin Amyloid Cardiopathy
MeSH:Polyneuropathies Amyloid Neuropathies Amyloid Neuropathies, Familial Amyloidosis
HPO:Amyloidosis Lattice corneal dystrophy Motor polyneuropathy Polyneuropathy

Even though more than 100 point mutations are known to cause the disease, the most common amino acid change is V30M. --- V30M ---

Primary Outcomes

Measure: Development of a new MS-based biomarker for the early and sensitive diagnosis of Transthyretin-Related Familial Amyloidotic Polyneuropathy from blood

Time: 36 months

Secondary Outcomes

Measure: Number of correctly identified patients with Transthyretin-Related Familial Amyloidotic Polyneuropathy

Time: 36 months

8 Project to Accelerate the Diagnosis of TTR Amyloidosis by Use of Molecular Biology in First Intention

Peripheral neuropathies are diseases that affect the nervous system outside the brain and spinal cord, their prevalence is 1% in the general population, the causes are extremely varied with more than 200 identified causes; the main ones are diabetes, excessive alcohol consumption and chemotherapy. They may be sometimes disabling but generally preserve autonomy. Transthyretin amyloidosis is a rare multisystematic hereditary disease with autosomal dominant transmission. They present usually as a peripheral neuropathies (FAP). They are due to a point mutation of the transthyretin gene (chr 18q). FAP is secondary to endoneurial amyloid deposits and are characterized by a slowly progressive sensory, motor and autonomic. FAP is the most severe hereditary polyneuropathy of the adult are irreversible and fatal within 5 to 12 years from onset. Most frequent mutation of TTR gene is located on the second exon; but more than 100 mutations have been reported. Prevalence of FAP is 1 per 1 million inhabitants. They have been reported until 1990s' in four endemic areas North of Portugal, Sweden, Japan and Majorca. In these areas, diagnosis is facilitated because of the stereotypical presentation : a length-dependent polyneuropathy with predominant involvement of thermal and pain sensations and autonomic dysfunction, early onset in the third decade and a predominant Met30 TTR mutation. Positive family history is frequent 85% (one of the parents is affected). Diagnosis requires detection of TTR mutation by molecular biology (blood sample) and characterization of amyloid deposit on labial salivary gland biopsy.

NCT03373370 Polyneuropathy Diagnosis Idiopathic Progressive Neuropathy
MeSH:Polyneuropathies Amyloidosis
HPO:Amyloidosis Motor polyneuropathy Polyneuropathy

Conversely to endemic areas, look for V30M mutation is not enough to exclude TTR-FAP, TTR gene sequencing is required. --- V30M ---

Primary Outcomes

Description: Rate of amyloidogenic TTR mutation in progressive idiopathic polyneuropathy

Measure: Rate of amyloidogenic TTR mutation

Time: 1 day

Secondary Outcomes

Description: Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : disabling neuropathy (including ataxic).

Measure: To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy

Time: 1 day

Description: Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy :variant Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Measure: To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy :variant Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Time: 1 day

Description: Rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : upper limb onset neuropathy.

Measure: To identify the rate of amyloidogenic TTR mutation in different subgroups of patients with neuropathy : upper limb onset neuropathy.

Time: 1 day

9 An Adaptive, Open-Label Study to Evaluate the Biodistribution of 89Zirconium-labelled GSK2398852 in the Heart and Other Organs of Patients With Transthyretin Cardiomyopathy (ATTR-CM) Using Positron Emission Tomography (PET) Imaging

The principal aim of this study is to investigate the cardiac uptake of 89Zr-GSK2398852 in subjects with transthyretin cardiomyopathy amyloidosis (ATTR-CM), and its biodistribution to other organs. Low doses of GSK2398852 will be co-administered at levels not high enough for therapeutic benefit. This study will be conducted in two parts: Part A and Part B. Subjects in Part A will participate in up to two dosing sessions and subjects in Part B will participate in one dosing session. Subjects will undergo up to 3 PET scans at varying intervals after 89Zr-GSK2398852 administration. The total duration of study will be approximately 3 to 4 months for subjects in Part A and approximately 2 months for subjects in Part B. Part B of the study will be triggered based on data obtained in Part A and other emerging data.

NCT03417830 Amyloidosis Drug: GSK2315698 (CPHPC) Drug: GSK2398852 (unlabeled anti-SAP mAb) Drug: 89Zr-GSK2398852 (89Zr-labeled anti-SAP mAb)
MeSH:Amyloidosis
HPO:Amyloidosis

b) Hereditary ATTR amyloidosis (example, TTR Val30Met) should have a known amyloidogenic TTR mutation demonstrated by genotyping and is recognized to be primarily associated with cardiomyopathy and one of the following: i) Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarized light in cardiac or other tissue biopsy and identification of TTR as the amyloid fibril protein either by immunohistochemistry or proteomic analysis. --- Val30Met ---

Primary Outcomes

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented. All treated population consisted of all participants who received at least one Anti-SAP treatment including 89Zr-GSK2398852.

Measure: Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb

Time: Session 1: Days 4, 5, 6 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented.

Measure: Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Session 2: Days 3, 4 and 5

Description: SUV in focal anatomical regions of the heart was planned to be measured.

Measure: Part B: Peak SUV in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb

Time: Days 3, 4 and 6

Description: SUV in focal anatomical regions of the heart was planned to be measured.

Measure: Part B: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Days 3, 4 and 6

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight.

Measure: Part A- Session 1: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb

Time: Session 1: Days 4, 5, 6 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight.

Measure: Part A- Session 2: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Session 2: Days 3, 4 and 5

Description: SUV of whole heart was planned to be measured.

Measure: Part B: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb

Time: Days 3, 4 and 6

Description: SUV of whole heart was planned to be measured.

Measure: Part B: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Days 3, 4 and 6

Secondary Outcomes

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as abdominal skin and skin of the back. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb

Time: Session 1: Days 4, 5, 6 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for thyroid gland-goitre hotspot. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyriod Gland-goitre Hotspot

Time: Session 1: Days 4 and 6

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as thyroid gland-goitre hotspot, abdominal skin and skin of the back. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Session 2: Days 3, 4 and 5

Description: SUV of focal radioactivity uptake for different organs/tissues was planned to be measured.

Measure: Part B: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb

Time: Days 3, 4 and 6

Description: SUV of focal radioactivity uptake for different organs/tissues was planned to be measured.

Measure: Part B: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Days 3, 4 and 6

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as adrenal gland, aorta, bone marrow, kidney, liver, spleen, abdominal region, brain, lung, parotid gland, and thigh. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb

Time: Session 1: Days 4, 5, 6 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for thyroid gland-goitre. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyroid Gland-goitre

Time: Session 1: Days 4 and 6

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for testes. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Testes

Time: Session 1: Days 4, 5 and 8

Description: SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as adrenal gland, aorta, bone marrow, kidney, liver, spleen, abdominal region, brain, lung, parotid gland, thigh, and thyroid gland- goitre. Mean SUV derived from PET images has been presented.

Measure: Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Session 2: Days 3, 4, and 5

Description: SUV of total radioactivity uptake for different organs/tissues was planned to be measured.

Measure: Part B: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb

Time: Days 3, 4 and 6

Description: SUV of total radioactivity uptake for different organs/tissues was planned to be measured.

Measure: Part B: Mean SUV of Total Radioactivity Uptake After an Anti-SAP mAb Dose Between 200 mg and <=500 mg

Time: Days 3, 4 and 6

Description: Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852). PK Population consisted of all participants from the All Treated Population for whom a PK sample was obtained and analyzed.

Measure: Part A: Maximum Concentration in Plasma (Cmax) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: Cmax of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A: Time Associated With Cmax (Tmax) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: Tmax of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A: Clearance of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: Clearance of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A: Terminal Half-life (T1/2) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: T1/2 of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A:Area Under the Concentration Time Curve Till Last Observation (AUC[0 to t]) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: AUC(0 to t) of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for PK analysis of total mAb (unlabelled GSK2398852 and 89Zr-GSK2398852).

Measure: Part A: Area Under the Concentration Time Curve Till Time Infinity (AUC[0 to Infinity]) of Total mAb

Time: Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7

Description: Blood samples were planned to be collected at indicated time points for PK analysis of total mAb.

Measure: Part B: AUC(0 to Infinity) of Total mAb

Time: Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: Cmax of 89Zr-GSK2398852 PKs of Radioactivity (Radio-PK)

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: Cmax of 89Zr-GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: Tmax of 89Zr- GSK2398852 Radio-PK

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: Tmax of 89Zr-GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: T1/2 of 89Zr- GSK2398852 Radio-PK

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: T1/2 of 89Zr- GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was measured using scintillation counter.

Measure: Part A: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK

Time: Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: Blood samples were planned to be collected at indicated time points for measurement of radioactivity. Radioactivity reflected the total concentration of 89Zr-GSK2398852 and its radioactive metabolites. Plasma radioactive concentration was planned to be measured by scintillation counter.

Measure: Part B: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK

Time: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least one dose of GSK2315698, GSK2398852 or 89Zr-GSK2398852.

Measure: Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time: Up to Day 26 of the last session

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; other important medical events which may require medical or surgical intervention.

Measure: Part B: Number of Participants With AEs and SAEs

Time: Up to Day 26

Description: Rash was graded as Grade 1 to Grade 4 based on symptoms and body surface area (BSA) affected; Grade 1: <10 percent (%) BSA and asymptomatic; Grade 2: 10-30% BSA and/or mild symptoms (pain, itch and burning); Grade 3: >30% BSA and/or moderate/severe symptoms (pain, itch and burning); and Grade 4: any rash with mucosal or systemic involvement (such as evidence of renal involvement).

Measure: Part A: Number of Participants With Skin Rashes

Time: Up to Day 26 of the last session

Description: Rash was planned to be graded as Grade 1 to Grade 4 based on symptoms and BSA affected; Grade 1: <10% BSA and asymptomatic; Grade 2: 10-30% BSA and/or mild symptoms (pain, itch and burning); Grade 3: >30% BSA and/or moderate/severe symptoms (pain, itch and burning); and Grade 4: any rash with mucosal or systemic involvement (such as evidence of renal involvement).

Measure: Part B: Number of Participants With Skin Rashes

Time: Up to Day 26

Description: The number of participants with any cardiovascular AEs i.e. any AE coded to the cardiovascular system organ class are presented.

Measure: Part A: Number of Participants With Cardiac Adverse Events

Time: Up to Day 26 of the last session

Description: The number of participants with any cardiovascular AEs i.e. any AE coded to the cardiovascular system organ class were planned to be reported.

Measure: Part B: Number of Participants With Cardiac Adverse Events

Time: Up to Day 26

Description: Number of participants with any infusion related reactions are presented.

Measure: Part A: Number of Participants With Infusion Related Reactions

Time: Up to Day 26 of the last session

Description: Number of participants with any infusion related reactions were planned to be reported.

Measure: Part B: Number of Participants With Infusion Related Reactions

Time: Up to Day 26

Description: Blood samples were collected to analyze the troponin T and NT-ProBNP at indicated time points. Baseline was considered as the latest assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP)

Time: Session 1: Baseline (Day 1 Pre-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26; Session 2: Day 1- Pre-dose, Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26

Description: Blood samples were planned to be collected to analyze the troponin T and NT-ProBNP at indicated time points. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part B: Change From Baseline in Cardiac Troponin T and NT-ProBNP

Time: Baseline and up to Day 26

Description: 12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Measure: Part A: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings

Time: Up to Day 26 of the last session

Description: 12-lead ECGs were planned to be measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal 12-lead ECG Findings

Time: Up to Day 26

Description: Continuous inpatient cardiac monitoring was performed via remote cardiac telemetry device. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Measure: Part A: Number of Participants With Abnormal Inpatient Cardiac Telemetry

Time: Up to Day 26 of the last session

Description: Continuous inpatient cardiac monitoring was planned to be performed via remote cardiac telemetry device.

Measure: Part B: Number of Participants With Abnormal Inpatient Cardiac Telemetry

Time: Up to Day 26

Description: Continuous outpatient cardiac monitoring was performed via remote cardiac bodyguardian telemetry device. Abnormal findings were categorized as CS and NCS. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Measure: Part A: Number of Participants With Abnormal Outpatient Cardiac Telemetry

Time: Up to Day 26 of the last session

Description: Continuous outpatient cardiac monitoring was planned to be performed via remote cardiac bodyguardian telemetry device.

Measure: Part B: Number of Participants With Abnormal Outpatient Cardiac Telemetry

Time: Up to Day 26

Description: SBP and DBP were measured in a semi-supine position after 5 minutes of rest for the participant. Potential Clinical Importance (PCI) ranges for the SBP and DBP were as follows: SBP- <90 and >180 millimeters of mercury (mmHg), and DBP- <30 and >110 mmHg.

Measure: Part A: Number of Participants With Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Time: Up to Day 26 of the last session

Description: SBP and DBP were planned to be measured in a semi-supine position after 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal SBP and DBP

Time: Up to Day 26

Description: Temperature was measured in a semi-supine position after 5 minutes of rest for the participant. Normal range for temperature was as follows: temperature- >37.5 degree celsius.

Measure: Part A: Number of Participants With Abnormal Temperature

Time: Up to Day 26 of the last session

Description: Temperature was planned to be measured in a semi-supine position after 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal Temperature

Time: Up to Day 26

Description: Respiratory rate was measured in a semi-supine position after 5 minutes of rest for the participant. Normal range for the respiratory rate was as follows: respiratory rate- <12 and >25 breaths per minute.

Measure: Part A: Number of Participants With Abnormal Respiratory Rate

Time: Up to Day 26 of the last session

Description: Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal Respiratory Rate

Time: Up to Day 26

Description: Pulse rate were measured in a semi-supine position after 5 minutes of rest for the participant. PCI range for the pulse rate was as follows: pulse rate- <35 and >140 beats per minute (bpm).

Measure: Part A: Number of Participants With Abnormal Pulse Rate

Time: Up to Day 26 of the last session

Description: Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest for the participant.

Measure: Part B: Number of Participants With Abnormal Pulse Rate

Time: Up to Day 26

Description: A full and brief physical examination was performed, including assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen).

Measure: Part A: Number of Participants With New Abnormal Physical Examination Findings

Time: Session 1: At screening (within 35 days of Anti-SAP treatment of session 1), Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11; Session 2: Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11

Description: A full and brief physical examination was planned to be performed, including assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen).

Measure: Part B: Number of Participants With New Abnormal Physical Examination Findings

Time: At screening (within 35 days of Anti-SAP treatment), Days 1, 3, 5, 8 and 11

Description: Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameters.

Measure: Part B: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameter: Hematocrit

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameter.

Measure: Part B: Change From Baseline in Hematology Parameter: Hematocrit

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameter: Hemoglobin

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameter.

Measure: Part B: Change From Baseline in Hematology Parameter: Hemoglobin

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameter.

Measure: Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameter.

Measure: Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the hematology parameters: Erythrocytes and Reticulocytes. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the hematology parameters.

Measure: Part B: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the chemistry parameters: Glucose, Calcium, Potassium, Sodium and Urea. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the chemistry parameters.

Measure: Part B: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the chemistry parameters: Albumin and Protein. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the chemistry parameters.

Measure: Part B: Change From Baseline in Chemistry Parameters: Albumin, Protein

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the chemistry parameters: ALP, ALT and AST. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the chemistry parameters.

Measure: Part B: Change From Baseline in Chemistry Parameters: ALP, ALT, AST

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Blood samples were collected to analyze the chemistry parameters: Direct Bilirubin, Bilirubin, Creatinine. Baseline was considered as the latest pre-dose assessment prior to first administration of either study drug, i.e. GSK2315698 or anti-SAP mAb (labelled or unlabelled) (Day 1, Pre-dose). Change from Baseline was calculated as post-Baseline value minus Baseline value.

Measure: Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine

Time: Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26

Description: Blood samples were planned to be collected to analyze the chemistry parameters.

Measure: Part B: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine

Time: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26

Description: Urine samples were collected to analyze urinalysis parameters including glucose, protein, blood and ketones.

Measure: Part A: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones

Time: Up to Day 26 of the last session

Description: Urine samples were collected to analyze urinalysis parameters including specific gravity and potential of hydrogen.

Measure: Part A: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen

Time: Up to Day 26 of the last session

Description: Urine samples were planned to be collected to analyze the urinalysis parameters.

Measure: Part B: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones

Time: Up to Day 26

Description: Urine samples were planned to be collected to analyze the urinalysis parameters.

Measure: Part B: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen

Time: Up to Day 26


HPO Nodes


HP:0011024: Abnormality of the gastrointestinal tract
Genes 2032
SMC1A FUS WHCR COL13A1 CTC1 MYO5B SYNJ1 COL1A1 COL5A1 TCF4 PTS REPS1 RRM2B C12ORF65 CFC1 CHRND EFL1 SDHC SETD5 SMO OCRL FOXP3 PACS1 PMS2 PNKD RET PTPN3 SETBP1 KY FCGR2C GLUD2 ASXL1 USP9X RAD51C MAFB KIF7 RECQL4 MAP2K1 PTCH2 ERAP1 POLG TP53 TGFB3 TSPAN7 PIEZO1 CLMP NFIX NDUFA6 PRKCG CTRC CHAMP1 EIF2AK3 EFEMP2 GLI2 ACTA1 MAPT GP9 VAMP1 TNFSF12 PITX2 KIAA0556 SMG9 ND3 XRCC2 ACOX1 CDKN2B ACTA1 DNM1 SOX10 ATXN3 MLH1 ACTA1 POLG RPL10 VAMP1 ERLIN2 CHRND TIMM8A NHP2 OPTN NFKB1 F13B FBLN5 TRNS1 H19 MSH3 TEK MNX1 MLH3 CDK4 SDHC VPS13A SLC9A6 SSR4 ZIC2 ACVRL1 MFF ANKRD11 SQSTM1 APC USP9X DNMT3B TPM2 UPF3B PAK3 HLA-DPA1 CHCHD10 GATA6 SDHB MAPT GBA2 ARL13B GCH1 MSH2 SLC25A13 AKR1D1 TOP3A BAAT CHEK2 FOXF1 STAT1 CYP7B1 SEMA3D ASPA AMACR GP1BB APC CCDC22 SLC52A2 SPG7 CTNS SOX2 BRCA1 RERE ZBTB24 RFWD3 NDUFS2 ASXL1 COL7A1 JAK2 MPI HMBS AGTR2 UROD F12 DKC1 ITGB3 ND5 PEX3 ACADVL PRPS1 GPC3 AGRN FTL XRCC1 UBA5 ERCC2 CAV1 RPGRIP1L ADAT3 MYC DMD CEP57 LMAN1 NUS1 FGF20 SDHB ALDH18A1 JAK2 EXT2 NTHL1 MEGF10 ACOX2 CCR6 MTOR DEAF1 MYLK KBTBD13 MAPT PANK2 HDAC8 LEMD3 TRAPPC12 COG4 SPINK5 BRCA2 DDHD2 F13A1 GLI3 GFI1B GPC3 RARB PIEZO2 MAPK1 KIFBP NSUN2 PHKG2 NBN PLXND1 STAT3 FAT4 PEX1 EOGT PHGDH SYT1 MKKS CDC6 EDN3 TANGO2 RET SCN4A ZFP57 GDNF COL7A1 AKT1 MUTYH ARMC9 SDHB CYP27A1 GABRA2 TERT SALL4 APC OSGEP ALDH18A1 PAX3 ITGA2 USP7 SLC2A2 LPIN2 SMC3 RB1 TBCE VAMP1 CD3G GLRA1 H19 PSEN1 NDUFAF3 MECP2 WNK1 TWIST2 RBM10 SRCAP PIK3CA LMNB1 KIFBP SHROOM4 SLC46A1 CHRM3 TXN2 TBX4 UBE2T SETX COL7A1 TPM3 SLC9A3 FLAD1 SMAD4 F10 ZSWIM6 SH3KBP1 CD79B PIGO LMNA FREM1 SLC9A7 ABCB1 FBN2 FUZ ASCL1 JUP GREB1L FAH KIT RIPK4 GDNF GATA6 ALG13 MRPS34 TRAPPC11 ARF1 DHCR24 RFX5 KLHL40 HNF1A KEAP1 CHD7 SLC52A3 TERC RRM2B EDNRB MITF PIK3C2A STAT6 SH2B1 C19ORF12 FGFR1 ARNT2 HTRA2 SLC19A2 IRF1 SEC23B PYROXD1 PARN SETD5 MGMT RPL10 DLX4 GP9 TCF3 NRXN1 MYO9A MECP2 HLA-B NOTCH2 GRIP1 DACT1 BUB1B MC1R ARID2 BRAF GAS1 MBTPS2 SOX10 PLG PARN SRC TRAPPC11 GDNF TPM2 TRMT10C RFXANK CAV1 SLC25A24 BMPR1A CASP8 DHCR7 TSPYL1 HNF1A ST3GAL5 RNASEH1 GRM1 TRIP13 IL23R MTTP PMS1 RFXAP KCNA2 ACTA1 ATXN1 FLNA ADNP FANCA MSH6 TTBK2 RRM2B TMPRSS6 POU6F2 APC SON PIK3CA FANCM ATP6V1A RET ARHGAP31 RBM8A FBXO7 HELLS EPCAM MEN1 TERT UBA5 HESX1 FA2H TRIP13 ZAP70 UBR1 CDKL5 AKT1 APC MYF6 NXN TBK1 RASGRP1 PPP2R3C MYORG MRE11 TCF4 ND5 IL10RA LRP2 HLA-B GTF2I DLC1 IRF5 KCNJ11 SYNGAP1 BTNL2 SLX4 OPA1 CYBA TP63 RAD21 KLHL7 DKC1 ORC4 VANGL1 ARPC1B PPP2R5D TCOF1 PCSK1 SRCAP CTNNB1 PLG PTCHD1 VWF USP27X ATXN3 PGAP2 WDR26 FANCI PYCR1 LYST TP53 UPB1 MUTYH ANTXR2 MMP1 PDX1 TANGO2 ATXN8OS KIF5A FIG4 BMPR1A WWOX RPL10 ERLIN2 CIITA SI GPC3 TPM3 PEX16 FOXG1 CYP7B1 PALLD VAMP1 PLCG2 GATA6 OSGEP ZNF711 TRNE PARS2 TTC7A FLNA OTX2 FARSB DDHD2 VAPB ARL3 NONO MED12 HNF4A NUP107 MLH3 SPG11 TMEM231 FMR1 AHI1 CHN1 CBLIF MYOD1 SEMA3E RERE CCN2 KLHL40 LAGE3 WT1 SRP54 ABCC8 DYNC2H1 ATRX GPC4 ALS2 IGHM ATP1A3 PHOX2B FGF12 BCR SPINK1 SDHD DDX59 IL6 MAP3K7 GABRD CTBP1 NOTCH1 ATP8B1 LAMC2 ADH1C PEX12 MKS1 IRAK1 EDN3 HCFC1 SACS DAXX TBK1 MST1 SLC6A9 TGFBR2 EXOC6B TCTN1 TNFSF12 FTL DOK7 TCF4 ITGB4 APC TRIM28 DNAJC21 MED17 NECTIN1 NAB2 RECQL4 KRAS CLCN4 EDN3 FLNA MVK C12ORF65 PIK3R5 FAM13A SFTPC CDKN1C TYMP KRAS GDAP2 PALB2 MED12 TK2 TMEM67 TEK RYR1 NHP2 MCM6 FGF8 IL1RAPL1 TDGF1 SNRPB QDPR CDCA7 CACNA1A IGH RET CAMTA1 SOX10 PGAP3 F8 CACNA1G ATP6 TRNQ LONP1 SIN3A PAX4 COL7A1 FGFR2 VPS35 PAK1 CC2D2A MDM2 SNCA NEK1 PQBP1 WAS ATXN3 CHMP2B CFTR KDM6A TGFBR1 FANCE ICOS RFX6 IL12A LIG4 KIF23 PARK7 HLA-DRB1 MKS1 CACNA1G DMP1 COQ4 ADA2 SMC1A GMPPA MLH1 GFI1 RET RNF125 COX7B FANCD2 SOX2 ACTB DYNC2H1 NEK1 DDX59 PALB2 GLA IL1B DSP TERT FOXE1 MAP1B IQSEC2 WDR73 ABL1 STXBP1 RFWD3 DLG1 NEUROG3 ND1 ERLIN2 TGM6 FXN CDKN1B NEK9 TNFRSF13B FANCL FRAS1 SPG21 ND6 WDR73 HIVEP2 SKI UBTF EXT2 SLC5A7 STAG1 FLT1 COMT GBA ACTB ATXN8 WASHC5 NAA10 WAS AK2 TRMT5 TMTC3 SOX10 TGFBR2 L1CAM MYO1H POLG PIGY CARS2 DDOST CHEK2 COX1 LIPA SQSTM1 AHI1 REST BMPR1A ACTG2 SIX3 ND4 PCNA SDHD SEC23B ZNF423 OPLAH FKRP CHRNA1 CNKSR2 PRKRA FANCB HMBS PTPN22 RAI1 HYOU1 HPGD C1QA ELN SLC25A1 CYP27A1 RPS6KA3 USF3 CAV1 ARV1 BUB3 H19-ICR AP2S1 FUS CCN2 CCR1 MTMR14 MAD2L2 EMC1 TMEM237 MSX1 PSPH FOXP3 CD19 TRNV WASHC5 SLC18A3 KIT HMGA2 CLCN1 AARS1 CEP57 TREX1 WNT4 WIPF1 SLC25A13 PEX12 TERC CHMP1A TGFB1 HTT CDKN2A GJB2 MET F5 BUB1 CTLA4 CDKN2C GPC1 GLMN HNF1B HLA-B BRCA1 SF3B4 FLCN SLC6A3 TNFAIP3 JAK3 PRKCD CDKL5 SUFU ABCD4 NGLY1 SNCAIP ATXN7 IRF2BPL COLQ PIGT L1CAM ARHGEF6 PEX26 GLRB POLR1D TK2 SIN3A CARMIL2 PITX2 WFS1 CISD2 LRRC8A LIMK1 SNCA WNT2B IRF6 SERPING1 TBL2 TWNK PMPCA TGIF1 POLR3B WDR4 CDC45 ENPP1 DGAT1 TWIST1 MEIS2 CPLANE1 STRA6 YY1 FCGR2A FBXL4 AFF4 SCN4A KIAA0586 FKTN SOX2 GREM1 RTEL1 NEUROD2 MMP1 ALG3 TP53 SLC6A8 ARNT2 HIRA ARSA EXOSC9 REV3L CCBE1 APP ELANE SLC35A2 COL18A1 RAD21 GDI1 DGUOK KMT2D ATXN2 POLG EDN3 SEC63 CHD4 PIGO NBN FANCF PLA2G6 DACT1 TP63 PLVAP FAS SIX1 TP53 HLA-DPB1 MATR3 PTRH2 ELN GNA11 RLIM TMEM138 SLC35A2 PANK2 RFXANK IRF5 ITGB4 ALS2 POLR1C KCNJ11 SCN3A DPP9 DNMT3B PIK3CA NLRC4 ASCC1 PTDSS1 IGF2R MPZ HNRNPU BTK TRNL1 EPCAM NDUFA9 FLNA ERGIC1 ATRX PRKCSH F9 PIK3R1 COL3A1 CHST14 ALS2 GRIN2D ECE1 NDUFAF2 GUCY2C KLF6 IQSEC2 SAA1 SPG7 CEP120 ATRX NEXMIF GJB6 ATM TNXB RTEL1 IRX5 GDF2 PMS2 HBB PUS3 PIGV GP1BB SALL4 LETM1 PNP COMP TRIM28 DCTN1 RAD51C CDC73 IL21 MYMK PIGL PIK3CA CEP120 KLHL41 FH HNF4A BCOR SLC30A2 MYD88 ABCA3 JAG1 TMEM70 NPM1 IKZF1 SCN9A PHKA2 DICER1 GNAQ CDH11 NOD2 LRRK2 WNT3 DNAJB6 FLVCR1 ZEB2 B3GALT6 TNXB PABPN1 MLXIPL COL13A1 VAC14 NEB SIK1 GUCY1A1 AP1S1 TRIP4 FGFR2 ECM1 TGFBR2 ALDOB KCNQ1OT1 POGZ TBP ARX PACS1 CAVIN1 PPARG ELP1 BAZ1B FRG1 IL12B TPRKB CHRNG TGFBR2 SCN8A ABCC6 IDH1 CPLX1 BCL10 KRAS HPCA SPP1 CYBB PTEN PMP22 CCND1 NOP10 MSH2 MUC5B GPHN NEXMIF PDP1 JAK2 MMEL1 MBTPS2 SYT2 IGHM MPI EDNRB POGZ RAB39B SYT1 GRIN2D MSX1 SCN3A LBR SPIB NIPBL SYNJ1 CISD2 TET2 PTPRJ MECP2 MPL GTF2IRD1 CREBBP MSR1 GP1BA PRKAR1A MID2 CSPP1 MYOT ATP7A PORCN IDH2 MYO5B ADAMTS3 CXORF56 MLX GATA1 TCTN3 SMAD7 NUP133 MAP2K2 SKIV2L TWNK TTC37 GBA KCNB1 CACNA1A SIX6 SPART TP53 SCN4A DOCK6 RBPJ RNF43 HSD3B7 VPS33A CTRC TRNL1 TGFB1 ANTXR2 STN1 TP53 TINF2 LINGO1 PHOX2B CR2 C11ORF95 PIEZO2 ABCB11 DSE KRT8 ZMPSTE24 LMOD1 GBA TOP3A AGA RPS20 GLIS3 BMPR1A BMPR1A ALDH18A1 CHST14 TRNK TBX1 SLC19A3 PEX11B EPCAM B2M ND1 MAP2K2 GRHL2 ELP1 INS SLC6A5 HBB MEN1 HFE COX2 EYA1 KRT18 MID1 PAX3 HABP2 CORIN CD81 ATXN3 MYH11 LRRK2 TP63 NCF2 H19 SDHD SH2B1 TBC1D23 NBN COG8 ACTG2 EDNRB DCC SPINK5 TJP2 GJB1 HRAS FCSK WDR60 DNM2 LCT CBS SNAI2 ACTG2 LMX1B NDUFB8 COX7B LAMB3 ERBB2 ADCY6 CEP41 FGG MEFV NCAPG2 INPP5E PIGN CDKN1A CCBE1 TMEM216 ACSL4 HMGA2 DCLRE1C AP1S1 SMC3 KANSL1 FGFR1 FREM1 F5 FGA FBN1 SOX5 CENPF UBQLN2 POLG2 SEC24C TSC1 FLNA NUP62 C1R B3GLCT NF1 POMT1 BRCA2 POLG ADAMTS3 PIGN HLA-DRB1 SLCO2A1 FREM1 HCN1 MMP21 APC SDHB LMNA ACVRL1 LMOD3 DIS3L2 PIGA VARS1 COL5A2 RET KIAA0319L FGFR2 CCR6 BMP2 MKKS APC IL1RN MITF LTBP4 FGFR1 TERT PSAP ERCC4 DLEC1 TSPYL1 LRP2 CLMP ARX BRCA2 SZT2 SBDS BRCA1 VPS13A MSH6 HFE TREM2 POLR3A SLC1A4 NPC1 DISP1 PEX5 ERCC4 SLC25A13 FIG4 HPS1 LARGE1 MTTP ELN ITGA6 YWHAG PTEN DCTN4 FBLN5 PEX10 AR RIPK1 DNAJC6 CHRM3 AXIN2 SNAP25 MUSK RAD51 HGSNAT SALL4 NONO KIAA0586 SLC2A10 AFG3L2 RREB1 TWNK ASAH1 REEP1 RPGRIP1L TARDBP FANCC PGM3 SMO EBF3 GYS2 KLLN POMT2 STXBP1 G6PC F11 RAI1 ABCC2 HLA-DRB1 DLL1 EPHX1 WRN SBDS OTC GP1BB EFL1 COX4I2 NOP56 ATP13A2 CYFIP2 CDKN2B DIS3L2 RAD51C ABCC6 NRTN FRMPD4 POLA1 CYBC1 HYLS1 SP110 UBR1 CASP10 C1R PRTN3 MSH2 RECQL4 SALL4 IL2RB RAC2 ITGA6 ATP7B PNLIP PDGFRL CCND1 STUB1 AXIN2 XYLT1 HOXD13 ENG CHAT CD109 IRGM CEL ZNF81 SLCO1B3 SETX NEFH FRAS1 TRNF ACTL6B TRAK1 PTEN SMPD1 MITF SDHC CLTC PRDM16 ATXN10 FLI1 STK11 COLQ ITCH CNTNAP2 FOXG1 SKI DHODH PKHD1 CHAT SYT14 CC2D2A CTCF ADD3 GLI3 ATRX SCO2 BAP1 ND4 SLC29A3 CD3E RELA UCHL1 B4GALNT1 ARFGEF2 SFTPA2 LBR DDC SRP54 SRP54 SMAD3 EPRS1 AKR1D1 KITLG PEX16 WWOX RERE BACH2 UBB MSH3 TYROBP ABCC6 WNT7A BIN1 FANCL PEX14 ATRX WFS1 POLE DDOST PIGW MYCN DDIT3 PMS1 KCNK9 SERPING1 NSD2 MNX1 GABRB2 POU2AF1 F7 SERPING1 CLIP2 QDPR CACNA1A GFPT1 CAVIN1 RFXAP NRXN1 MUTYH ACD MEOX1 NDUFS3 GNAS GNS CHRNA1 ATXN8 ARX NDUFB11 DACT1 MATR3 POLG2 SHH TUBB4A FOXH1 ATP11A SNAI2 CRYAB TNFRSF13C CEP120 ATAD1 TBC1D24 PROKR2 MAP3K7 UBAC2 POLG NOTCH2 USB1 TSC2 TMEM67 EDN3 UBE3B HSD3B7 RMRP PRSS1 KCNQ1 SCN4A COQ2 HLA-B NGLY1 DNAJC13 NTNG1 BCOR NCF1 ROR2 ACD SLC6A8 ERMARD TGFB2 INTU LIFR ATN1 FGA PIGV ITGB2 B9D1 KRAS NFKBIA LRP12 RNASEH1 POLG PLEC APC ITGB4 USP9X PIGN SDHA XIAP PPP3CA SMAD4 COL7A1 GMPPA BRCA2 DLL4 MYPN DSP SDHB NUP214 RMRP SDHC DNAJB6 MGME1 SLC39A4 TRNW CHEK2 RPL11 EMC1 IL2RA SLC37A4 ATXN8OS STUB1 ARID1B KMT2A SAMD9 TRNH ATP1A3 ATXN7 AXIN2 RPS19 GPR35 TBX1 GDF6 ATP6 TFAP2A AP3B2 HCCS PRKCD NEB JAK2 IFNGR1 TBX3 RAPSN FLVCR1 SCARB2 SEMA3C FMR1 AKT1 CCDC47 TBX3 TCIRG1 KAT6A TIMM8A NEFH PTCH1 AP1B1 SERPINA1 FAN1 CDC73 IRF5 FAS FERMT1 CYP7B1 ADAM17 APC CTC1 PLEC NTRK2 VAC14 NPHP3 MDM2 CFTR MYH8 KCND3 XRCC4 SOX3 PLA2G4A BDNF KLF11 ADAR RPS6KA3 IGLL1 CRKL GABBR2 FREM2 VCP POLG ENG PRSS1 TBP NECAP1 PTCH1 SMC1A MACF1 TARDBP MEFV SPG7 DKK1 NCF4 RELA CTHRC1 ATP7A PLA2G6 PEX13 POLR3A CLCA4 JAK3 ABCB4 TNFSF15 CEP104 APPL1 ARHGAP29 PEX6 YARS2 BSCL2 AHCY RAD51D SOX10 SKI IL12A MCOLN1 WT1 FASLG RSPO2 FOXF1 STOX1 PHOX2B BUB1 SOD1 PLAA ENG SDHD CTNNB1 CNTNAP1 HSPA9 ORC1 COG7 THOC6 MYH7 POLR3A VPS13C TRNL1 SLC2A10 KCNA2 GPIHBP1 STS FGFR3 IL12A-AS1 CDH1 WFS1 MYH3 GPC4 SMAD4 RAD50 SUFU MKS1 IL10RB AMER1 GRHL3 HDAC8 RHBDF2 PEX2 BRAF NEB SETBP1 KMT2A ORC6 MASP2 SLC5A7 ASCL1 KRAS ZFYVE26 DCHS1 NEDD4L POLD1 DVL3 STN1 SLC52A3 PTEN SEMA4A UFD1 RARS1 PODXL SMAD4 LRBA FLNB B3GLCT FGFRL1 FGFR2 DNAJC21 ITGA2B FOS EDN3 SERPINH1 DGUOK BRCA2 NFKB2 SNCA NOP10 NDUFB11 JMJD1C FGB PALB2 FAT4 TTC7A ITGA2B C9ORF72 C2CD3 HPRT1 GABRA5 SLC18A3 RAD21 SLC25A22 REEP1 RTTN TK2 CDK4 NCF1 RAD51 EWSR1 AAAS GIGYF2 INHBA FARS2 PEX19 PORCN SEMA3E FGB ZIC3 NEB HYMAI TAF1 NPHP3 IRF6 LBR TNPO3 SLC25A4 CHRNE LRP5 DPYS SYT14 HOXB1 MLH1 SDHC LAMB2 WDR34 SLC52A2 SPECC1L LAMA3 FLCN TRAPPC12 KLHL41 TCF4 GDNF SPG21 STAT4 CTNNB1 STK11 CSPP1 EP300 FGFR2 FGG ASCC1 AMACR GMNN SYP ND2 CDH1 LAMA2 ATXN2 ADAMTS2 GBA FAT4 ZNF41 BLM CDKN2A TNFRSF1A MTM1 SNCA POLD1 ISL1 TPM3 FGFR3 MSH2 TUBB4A NUP88 SLC6A19 ABCC8 PITX2 AGGF1 NALCN PTS SALL4 CDH1 CDKN1B ATXN1 KIT FGFR2 LMNB1 UBTF TECPR2 PPP2R5D MECR TGFB1 PSAP BMPR1A CYBB FANCB STAC3 RNF43 AICDA TERF2IP NDUFS1 SLC6A3 ACTA2 CHRNE HLA-DRB1 ITGA8 MSH6 EIF4G1 WRAP53 PANK2 STXBP1 RFC2 PDGFRA KIT ATP2A2 CEP41 SPINT2 CFTR ZIC3 CCNQ IDS F2 ND6 NOTCH3 TUBB6 FOXC1 INPP5E PIEZO2 EP300 XYLT2 TRNW DLL4 NODAL DOCK8 PFN1 MBTPS2 PHOX2B PRPH ZFPM2 SPINK1 LIPA PAH KLRC4 ALS2 TMEM237 SLC30A10 MYOT POLE NECTIN1 PLAGL1 KCNAB2 PRKN CHD7 BRAF AGPAT2 ENPP1 POLG KIT PPM1D FGFR2 LAMB3 SHANK3 SLC37A4 SLC1A2 MCFD2 CEP290 KIF1A MAPT ALDH18A1 TAF1 SHPK SLCO1B1 DNM1L EP300 SPRTN WNT3 PIBF1 TCTN2 GNAO1 COL14A1 RHBDF2 DAB1 TWNK RETREG1 RYR1 CTNND1 CNTNAP1 HNRNPH2 WT1 NCF2 RAI1 AFF4 LIG4 SURF1 MAPT SELENON TRIP4 GDF3 ITGB3 SHANK3 BBS1 STAG1 ATP1A3 NPHP1 CD79A EFTUD2 CDH1 BRIP1 TWIST2 SLC5A1 IGF2 NIPBL PDGFRA PRKRA BLNK ALG8 PCGF2 MEN1 BRIP1 RNF6 DHCR7 BUB1B RET CNKSR2 POLR3B ACTA1 DYSF AFG3L2 SLC10A2 GCK NOTCH1 KCNK9 NCF4 SMAD4 STAT1 TTC37 TAF1 IL12RB1 CAMK2B C4A TNFRSF13B NR4A2 EDNRB POT1 INPP5E MINPP1 PTPN22 TRNK ATP7A CIITA CLCN4 MAGEL2 STX1A EHMT1 BARD1 IGF2 LIPA MYO9A EEF1A2 FLII TMEM237 PKD1 NOP56 SKIV2L PRNP SFTPA1 CXCR4 SAR1B RTEL1 POLG SLC46A1 CACNA1B DLG3 CD55 TPM3 GBE1 CCDC28B TJP2 TLR4 PLP1 PIK3CA NPC2 FANCB COG4 SDHB CCND1 IL10 ITGB3 EDNRB NALCN NOTCH3 SAR1B F5 PTEN GEMIN4 CASP10 EXTL3 MCEE MAPT STAT4 NPHS1 PLEC ARVCF FTSJ1 RAD51 GBA COX3 ZAP70 AAAS PDGFRB PLAA NUP62 CCNQ PHOX2B TYMP COL5A1 PTF1A IARS2 SEC23A COG6 PIK3CA SLC7A7 CYBA LAMC2 HFE RFX5 MS4A1 PUF60 DHDDS DMPK AIRE TRNS2 HRAS HDAC4 FANCG WDR35 KLHL7 AXIN1 EDNRB FLCN BLK NRAS SLC9A6 RRM2B IFT80 AAGAB GABRG2 ATXN8OS FAH BMP4 ITGA2B CDH11 NEUROD1 PINK1 MLH1 FANCB PSTPIP1 SLC13A5 KLHL41 GP1BB KAT6B MYRF SLC52A3 STX3 DCHS1 TTC7A ECE1 HCCS MECP2 APC PRSS2 PLOD1 SALL1 KAT6B GP1BA PANK2 LAMA3 FAS PDE8B SALL1 TP53RK TBCD FREM1 CDON MECP2 GP1BA CHCHD10 CD96 KCNC3 SNAI2 MED12 VANGL1 CDKN2A
Protein Mutations 1
C10D
HP:0001638: Cardiomyopathy
Genes 716
NDUFS7 PEX5 PDGFRA LMNA TCAP TPM1 EPG5 SGCB DOLK GPC4 PCCB XK MLX CPT2 GPR101 VCL TAZ MAP2K2 YARS2 TWNK RRM2B SDHA MC2R TMPO BRAF PRKAG2 BSCL2 AHCY TNNC1 NEU1 XRCC4 IDUA VPS33A GABRD TRNL1 CAP2 MYO18B IDH2 NDUFA10 GYG1 VCL LAMC2 NDUFV2 SLC25A4 TNNI3K RNU4ATAC CHKB DES MYH7 JUP BAG3 PEX10 MYBPC3 HADHA TRNL1 CRYAB SLC2A10 LMNA RAF1 TMEM43 MYOT HADHA WFS1 MAP2K1 TACO1 HADHA MYH7 PPA2 ACTN2 HSD17B10 GPC4 PEX19 NDUFB11 MYLK2 COX10 SARDH NAGA TRNK MRPL3 ATP6 TMEM70 GMPPB ND1 DES MAP2K2 KLF1 POMT2 NDUFS1 CAV3 KRAS DPM3 HFE COX2 FASTKD2 PTPN11 ITPA ANK1 CDKN1C FKTN ACTA1 TK2 RYR1 BSCL2 RNASEH2A ATP5F1D SHOC2 SDHA NDUFS3 FHL1 ANO5 HNRNPA2B1 PARS2 PPCS NDUFA11 ND3 XRCC2 FOS TPM3 RBCK1 TNNT2 ELAC2 TRNQ ACTA1 COX6B1 NDUFB11 COL7A1 HRAS PALB2 NDUFB8 COX7B ABCC9 COX8A ND3 TGFB3 ACADS TMEM126B DSP LDB3 FANCE DES RMND1 HADHA PSEN2 NDUFS2 TTR NDUFS2 TRNS1 H19 ARSB LAMP2 SLC25A20 PTPN11 RAD51 ALMS1 RAF1 NDUFS2 TNNT2 FKTN TAZ POLG2 COQ4 NRAS RAF1 HNRNPA1 RAB3GAP2 SGCB ACTC1 SYNE1 MYH7 NF1 HACD1 MYL3 AGK POLG COX7B PEX7 FANCD2 SYNE2 SLC25A4 KCNJ8 GLA ANKRD11 FHL1 SYNE2 DSP TERT USP9X TPM2 LAMA3 NDUFA2 SDHA SDHB MRPS22 ND1 NAXD DMD FXN SPEG GNPTAB SHOC2 IDUA FKRP NDUFA12 NDUFAF4 BMP2 ND6 NNT COG7 ECHS1 GATAD1 FHL2 NDUFV2 LDB3 TOP3A ND2 SLC25A4 POMT1 ERCC4 HADHB PNPLA2 CSRP3 LAMA2 DLD MTFMT SUFU SCO2 VPS13A NEBL POMK FLNC RNF113A HMGCL MYH6 AGK TSFM MAP2K1 TNNI3 BRCA1 TRNS1 GATA4 MRPL44 FIG4 LAMA4 RFWD3 PCCA NDUFS2 PRKAG2 COX1 DTNA HPS1 DMD TNNT2 BRAF LMNA COL7A1 FXN LMNA NBAS TXNRD2 ND5 NDUFAF6 PEX14 ACADVL EMD ND4 WARS2 ANKS6 TMEM126A TREX1 GPC3 FKRP PKP2 ATAD3A NUP107 MEN1 LMNA CAV1 HADHB HGSNAT MMUT ELN PEX26 TGFB1 PMM2 FLNC H19-ICR NDUFA11 TWNK LDB3 PLN SLC19A3 SCN5A RAF1 FOXRED1 NEXN NDUFAF2 FANCC TPI1 HJV PET100 MAD2L2 SLC25A3 KBTBD13 ERCC2 NDUFB9 MMUT DOLK PPARG FOXRED1 NDUFS7 TRNV PLN PCCA TAPT1 COX14 SCN5A CSRP3 ACAD9 VCP KRAS RFC2 ERBB3 GTPBP3 ERCC3 GSN NDUFAF1 DSC2 LAMP2 TRNN NDUFV1 LMNA TXNRD2 PTPN11 MYL2 ND6 TRNT PET100 CPT1A FKTN ABCC9 XYLT1 HLA-B XYLT2 PEX3 COX15 DSG2 NDUFA10 DSG2 DPM3 SDHD TRNW TRNF JUP TPM2 OPA1 MICOS13 DNAJC19 NDUFA6 NDUFS1 PNPLA2 NAGA PHYH DNAJC19 PMM2 LMNA NDUFAF4 ACTA1 LAMA4 PRDM16 ND2 EYA4 MLYCD PPCS PEX6 PIGT CRYAB GNE NDUFAF1 MYBPC3 ALG1 SLC30A10 SKI NDUFAF3 TAZ TTN KCNAB2 ACADVL INSR SLC25A3 CPT2 BRAF AGPAT2 TNNI3 ENPP1 WFS1 CISD2 MYH7 COA8 SELENON POMT1 LIMK1 MRAP PRKAG2 SCO2 TBL2 PEX2 RIT1 MYSM1 UBE2T GJA5 USP8 ND4 LAMB3 TRNT1 TACO1 DMD RNASEH2B ACTN2 SPTB NDUFA9 TWNK CSRP3 FLAD1 AARS2 ATPAF2 EPG5 MTO1 SPTA1 FBXL4 RERE NDUFS4 SGCD TNNC1 LDB3 MAP3K20 JUP ABCC6 CPT2 GATA5 FAH NDUFS3 ACAD9 COX20 VCL ACAD8 GSN NDUFAF2 FANCL SDHA FKTN TWNK RRM2B GMPPB IFIH1 SOS1 SLC40A1 MYH7 FHL1 FOXRED1 PEX7 COX15 SURF1 TTN SELENON TRIP4 GMPPB DCAF8 KCNH1 NEK8 NDUFS6 TTN ACADL HADH NDUFAF3 POLG CLIP2 NDUFV1 BRIP1 SLC19A2 DSG2 TNNT2 KRAS BAG3 JUP GYS1 TNNI3 POMGNT1 IGF2 FANCF ANKRD1 COA6 ADCY5 TMEM126B LIAS EYA4 PCCB ACTC1 GNS ACTA1 HAMP C1QBP DSP NDUFB11 ATAD3A ADCY5 BRAF ADAR GTF2E2 TIMMDC1 STAR FKRP CRYAB LMNA TPM2 CRYAB MYOZ2 NDUFAF5 SGSH ACAD8 TRNK RNASEH1 AGL TTR IDUA NDUFS8 CPT2 SLC25A20 NEXN ABHD5 RMRP COA5 KCNQ1 PEX7 ITGA7 COQ2 NDUFS8 ND1 FANCA NDUFA13 TRNL1 POMT1 NDUFS4 MYH7 SLC4A1 TMEM43 GTF2H5 FANCM TARS1 MYH6 CLN3 POLG DLD AHCY TPM3 GBE1 SDHAF1 PSEN1 MYL2 CDH23 BAG3 RAF1 NDUFB10 NDUFAF5 SGCA KAT6B MYH6 POLG UBR1 PEX13 MPLKIP TNNI3 PSEN1 MYBPC3 MGME1 NEB PEX11B SDHA TPM1 RBM20 LTBP4 ALMS1 COA8 HBB BBS2 POMT2 AIP PDHA1 MIB1 DSP ALG1 BRCA2 CENPE NDUFS4 ND5 HAMP NDUFB11 MYPN TTPA POMT1 RAD51C MGME1 GTF2I EPB42 TRNW PEX1 PPP1CB COX3 MYPN RNU4ATAC BCS1L FTO RNASEH2C MYPN LMNA TFR2 GUSB TMEM70 NDUFA4 SLX4 TRNH ATP6V1A D2HGDH NEXN GATAD1 PSEN2 NUP107 HFE GLB1 SCO1 NDUFA2 ATP6 HCCS TNNC1 NEB NAGLU AIP TRNS2 HRAS PIGT SGCD FANCG FANCI TTN SAMHD1 NUBPL PGM1 RBM20 ABCC9 MMP1 TANGO2 MRPS14 KCNQ1OT1 CAVIN1 PLN PPARG FIG4 LMNA MIPEP ACTC1 BAZ1B FHL1 DES MYH7 IL12B LMNA PRDM16 NDUFV2 ABCC6 SLC22A5 RYR2 ATP5F1E FANCB NDUFS8 MAP2K1 SDHAF1 GPC3 HADH HJV NPPA TPM3 KLHL41 MYPN AIP BOLA3 TRNE GTPBP3 DMD HCCS TCAP LIPT1 VAC14 SLC25A4 LIMS2 PEX16 DSP NDUFB3 JPH2 VPS33A SURF1 CLPB TNNI3 MYOT TAF1A PRDM16 TPM1 MYH6 POLG NDUFA1 GTF2IRD1 PEX12 SDHD DMD AGPAT2 TRNK SMC1A PHYH
HP:0001635: Congestive heart failure
Genes 260
TRNF TF JUP TPM1 EPG5 EPAS1 DNAJC19 PHYH LMNA ND5 TCF4 ATXN7 TRNS2 VCL EYA4 TAZ NDUFAF1 ABCC6 BSCL2 NDUFAF3 MYH7 TTN SCN5A VPS33A SLC25A3 TRNL1 AGPAT2 TNNI3 COX3 MYH7 LIMK1 PRKAG2 SCO2 TBL2 MYSM1 ENG TRNS1 TNNI3K DMD KIF1B DES COG7 GBA JUP BAG3 MST1 TRNF TRNL1 PSMB8 SLC2A10 TMEM43 VHL HADHA SCN1B CDH23 MYH7 PPA2 MDH2 PTEN MYLK2 SGCD CLIC2 LDB3 IKBKG CLIC2 ACAD9 PRKAR1A TMEM70 TRNW HBA1 ND1 DES CYTB SDHB NSMCE2 HBB CAV3 TPI1 HFE COX2 CASR PEX7 AFF4 MECP2 CEP19 SURF1 EFEMP2 TRIP4 SF3B1 SDHC CLIP2 TNNT2 HNRNPA2B1 NDUFB11 FOS ADCY5 EYA4 CP TMEM127 ATP5F1A CACNA1S ELAC2 ND1 TRNQ ACTC1 SLC25A26 HAMP DLST NDUFB8 ADCY5 SMAD4 TRPM4 STAT1 TMEM127 DSP CAV1 SDHD HADHA TRNK FBLN5 TRNS1 FGD1 ALMS1 COX2 ENPP1 HNRNPA1 TUBB RAB3GAP2 TRNK MYL3 FLNA HLA-DRB1 RASA1 ADAMTSL2 GLA RET VHL SELENON SDHB PRKAR1A SLC25A11 CYTB TRNV LMNA LMNA SDHAF2 ACVRL1 GLA GNPTAB PSEN1 BMP2 TRNL1 GDF2 ALMS1 FBN1 DSP HADHB STRADA PNPLA2 SNAP29 PSMB8 GTF2I SDHD TRNW COX3 GJA1 MYH6 BCHE LMNA MYD88 NDUFS2 TRNH ATP6V1A COX1 FH DTNA HBA2 GATAD1 PSEN2 FGFR3 HFE LMNA GLB1 RPS19 FXN GPR35 AGGF1 ND5 SDHD ND4 KCNJ5 TRNQ TRNS2 CAV1 HADHB TRIM37 ELN TET2 KIF1B RBM20 COL1A2 LMNA COX1 RYR1 CAVIN1 CCR6 SCN4A PPARG FLNC BAZ1B CCN2 MYH7 HJV MAX LMNA VHL IRF5 ABCC6 SLC22A5 RET MYPN MYH7 PPARG WRN PLN COL1A1 TRNE MAPRE2 GTPBP3 ACAD9 VCP SLC17A5 SDHB RFC2 GTPBP3 SLC19A2 PLOD1 RET SDHA TTN ND6 DSP LMNA MAX IDS FGF23 ND6 GDNF PRDM16 IFIH1 NKX2-5 XYLT1 XYLT2 ENG GTF2IRD1 GNPTAB TRNC TRNK PRKAR1A GNA11
SNP 0