SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


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 2049
CTBP1 PRSS1 EDN3 INSR ELP1 KCNAB2 ARHGAP31 FGFR3 ABCB1 EPCAM AICDA POLG ADCY6 CASP10 TBP GPR35 TK2 MYLK TMEM138 SLC52A3 CHMP1A SCN8A ARHGEF6 HCCS SNCA GLA WDR35 CCR1 WWOX CCR6 TTC7A GFPT1 PTCH1 PTF1A NUP133 LAMC2 NR4A2 VPS13A B9D1 PIK3CA NUP62 AXIN1 ARX AP1B1 ERBB2 SERPINA1 INS CDH1 CEP57 CAMK2B BSCL2 PIEZO2 BCOR KIT REEP1 TCTN2 SLX4 MECP2 MITF CHRNG BCOR ACADVL SFTPC SLC19A2 HGSNAT BUB3 DHODH LIPA NALCN ANTXR2 ARL3 ATRX SCARB2 FCGR2A SQSTM1 PLP1 LYST DDHD2 FOXF1 EDNRB ARSA F11 TEK AP1S1 SI DICER1 SFTPA2 MYO9A RHBDF2 MDM2 WT1 MMP1 IGHM FGF8 SALL4 MTTP DGUOK SRP54 ATXN8OS NEXMIF DSP COLQ EEF1A2 TUBB4A LTBP4 ACTA2 UFD1 LETM1 DDC TDGF1 KIAA0586 ZFYVE26 CTC1 TARDBP RFXANK SH2B1 RARS1 ICOS MECP2 LPIN2 IRF5 PTPRJ GPC1 KITLG JAK2 WIPF1 RAD50 SLC9A6 HBB LRRK2 PPP2R5D ATP7B EP300 HFE FREM1 CLTC VANGL1 ANKRD11 DEAF1 SPG7 SIN3A PYGM HESX1 INAVA HLA-DRB1 ACTG2 WAS DACT1 DOK7 FGFR2 ZFP57 IL23R FANCL DIS3L2 LBR EFTUD2 DCHS1 UBA5 SMAD4 NOP56 NEK1 ERLIN2 DNMT3B DMPK BRCA1 BCR CEP41 MRPS34 GP1BA IQSEC2 RETREG1 CARS2 MSH6 CREBBP OTC POLG APC PLG STK11 SLC25A1 PARS2 HBB MITF IGLL1 IRAK1 ATRX TPM3 DNAJB6 ND6 AKT1 RRM2B TERT TRAPPC12 TP53 BMPR1A MAD2L2 ZMPSTE24 ATXN7 MED12 CHAMP1 FOXP3 RTEL1 APC IL12RB1 TRNL1 NODAL MSH6 TANGO2 DYNC2H1 PEX13 SLC18A3 SPG7 SNCA NEK1 MEOX1 CAV1 FA2H CDKN1C USP7 PTEN ERMARD RFWD3 PIGN RPL10 COL5A2 BLM NDUFAF3 H19 ABL1 PYGL IRF1 CHRM3 CDC45 FTL GDAP2 TCF4 HIVEP2 MAPT APC GRHL3 DLL1 FLVCR1 PRKCD PIK3CA CDC6 RECQL4 MSH3 MED12 BRCA2 PALB2 SDHC SDHD DNM1 COL13A1 KIT CHCHD10 MNX1 RTTN KEAP1 APC PMS2 FKRP POLG ABCC6 SDHB TGFB3 UBTF TRNF EPHX1 SCN4A CCDC28B ERLIN2 APC ATXN8OS AURKA AMER1 FUS PRDM16 PLA2G6 AP2S1 ADAMTS3 TP53 PLOD1 GMNN HYOU1 ITGB4 MYF6 TPM3 SPG11 SLC9A6 MBTPS2 COG4 RREB1 CHRNE SDHC NPHP3 CFTR PAH SLC5A1 XRCC1 WWOX WASHC5 AKR1D1 PHOX2B FAT4 PITX2 VAMP1 RET MEN1 PEX19 ITGA2 NXN BDNF LMOD1 SOX10 FBLN5 ANTXR2 TMTC3 HELLS RAD51D KIF5A DYNC2I1 KCNJ11 KRAS FLT1 RECQL4 SP110 PPP2R3C HLA-B ABCA3 CNTNAP1 DGAT1 FAS CNKSR2 MBTPS2 ATXN8 MMP21 DISP1 FCSK PDGFRL SOX10 RIPK4 LRP2 AXIN2 PTPN22 SEMA4A TWNK NRAS EDN3 FLAD1 RTEL1 ASCL1 CYFIP2 GRM1 TLR2 PIK3CA CENPF CCBE1 VPS35 GJB1 ASXL1 CDC73 APC SOX2 WT1 ATXN3 MKS1 ATP7A TWIST2 F8 TBX4 UBR1 SMAD4 TRIM28 GP1BB REV3L NEDD4L CYP7B1 TGFB1 PIK3CA EPRS1 SBDS ATP1A3 GFI1 RAD51 PTCHD1 ACSL4 ATN1 SLC6A8 PEX11B TERT ADAT3 B4GALNT1 LIG4 MAPT NFKB1 GBA TWIST1 RNF43 ALG3 VAMP1 BMPR1A FGFR2 TET2 POLR3B EXT2 SMC3 HRAS SLC25A22 TBK1 MAP2K2 MECR APC XIAP RAC2 CDC73 MS4A1 ERGIC1 BRAF CRKL CDK4 RELA PTS APP GRHL2 STAT4 GFI1B HOXB1 CBS PIGO TCOF1 ALS2 RLIM ADAMTS3 APC PIGL ACTB RAD51C PAK3 ENG GUCY2C L1CAM TUBB4A PRNP TMEM67 GLMN TBX1 IL12A MLH1 PTPN12 MLH3 SETD5 ITGA2B CCDC22 APPL1 COL14A1 POGZ PHKG2 DDOST ND4 CNTNAP2 PARN SMAD4 UBB PRKAR1A PIGW DMD KRT18 POLG GP1BB NRTN PHKA2 ITGA8 UPB1 HLA-DRB1 TRNV PSAP TGFBR1 MSH2 AHI1 KIF7 NDUFB11 RAI1 C12ORF65 PDE8B RPL11 SCN3A TNFSF15 SLC6A3 FLNA CCN2 FAT4 KDM6A TBX3 RPS6KA3 EFL1 OSGEP PPM1D PIGY TMEM231 LIMK1 SOX3 LBR MINPP1 PDX1 PSAP HNF1A KIFBP CD79A AFF4 LIG4 SLC6A9 ARL6 DNM2 ELN KIT GBE1 RRM2B PRSS2 GNAQ ADA2 FGFRL1 SDHC GDNF PDP1 HABP2 FAM13A SALL4 WDR4 SYNJ1 SAA1 ADD3 CDKL5 BMPR1A CHRNA1 TRAK1 KANSL1 PLG SLC5A7 PHGDH PSTPIP1 ROR2 HMGA2 NCF4 POLG TNFRSF13B TRNQ CDKN2A POLR1D XYLT2 ATXN3 IL1RAPL1 GABRA2 KMT2A CYBC1 MTOR SRCAP MYD88 COL13A1 LMAN1 MYMK B2M DOCK6 LRP2 MGMT GCH1 TOP3A F2 SIX3 FRAS1 PABPN1 EDN3 IRF5 SDHD SOX2 SKI GP1BB CORIN PITX2 AGGF1 RPGRIP1L DLL4 C1R RERE H19-ICR MAPK1 SPINK5 LAMA2 MYH8 FANCB TGFB1 GBA RAD51 AR HNRNPH2 SLC18A3 SELENON UBR1 TRIM28 FOS PUS3 TSPAN7 HFE TSPYL1 C2CD3 TNFAIP3 SPP1 CNTNAP1 SEMA3D PLEC IGF2 LEMD3 HLA-DPB1 RFXAP TMEM216 FARS2 PFN1 TRNS1 TECPR2 LMNA ADAMTS2 ARX TWNK TRNH PIGV C9ORF72 CACNA1A TMEM237 PALB2 MAPT ALS2 RPL10 MYO9A PEX14 IL12A ERCC4 SLC6A5 CTHRC1 CDH11 REST CAV1 CC2D2A SRP54 DHCR24 ABCC8 ACD STN1 ARNT2 NSD2 ITGA6 ATXN2 ATP2A2 NECAP1 BCL10 SKIV2L G6PC PDGFRB WNK1 ENPP1 STAT6 FGB NEUROD1 BRCA2 SOD1 LAMC2 ZBTB24 STXBP1 SYT1 COX1 CCND1 NSUN2 TYMP ZFPM2 RPGRIP1L RAD51C LMNA COL7A1 ITCH CD3E MYO5B BRCA1 ATP7A RYR1 PRTN3 EMC1 PYCR1 CISD2 ZEB2 CYBB POLD1 HOXD13 SNAI2 PTS KCNA2 ZNF711 BMP2 ELN MUTYH PLVAP F10 RYR1 TERT SLC25A24 FBXO7 RET AHCY COL5A1 FAT4 KIT GATA6 KCNQ1OT1 EDNRB RNF6 GDI1 PIK3C2A CAV1 STRA6 PIEZO1 MMEL1 BUB1 CIITA ABCC6 COX2 WNT4 STOX1 IRF5 CDKN2B HPRT1 USP9X INTU HDAC4 SPECC1L CTNS MGME1 FAS TPM2 CCND1 CPLANE1 H19-ICR ODC1 SAR1B PEX2 TERT BRCA1 SON COL7A1 DPP9 STAT1 MTM1 BRAF OPA1 IRF6 LIFR RRM2B GBA CBL SDHB TRIP4 KLHL7 SDHD SLC46A1 NUP62 ATXN3 ADH1C NOP10 MPI IFT80 SEC63 SPRTN ACTL6B GDF6 FTSJ1 CDH1 TREX1 SRCAP TOP3A MDM2 FUS RIPK1 COX7B IGHM CLMP MYH11 EMC1 SAMD9 PTEN GLI3 MAPT SLC29A3 SERPING1 GP1BA COG8 ADAM17 ATP1A3 PANK2 FBLN5 NEB PNLIP CSPP1 CD19 GNAO1 CXORF56 KLHL41 DCTN4 ECE1 FRAS1 BLK EDNRB SEMA3E FANCF NTRK2 MYO1H AKR1D1 PIK3R5 TBX3 CHD7 CFTR CC2D2A NBN MAN2B1 CHRND ZIC2 MYO5B SNAI2 PLEC SH3KBP1 KAT6A FANCG FUZ HDAC8 NIPBL YY1 ASXL1 NEB MYOT KATNIP ITGA2B PTRH2 SLC2A10 FCGR2C COQ2 CDKL5 ALDOB ALDH18A1 FANCI TNFRSF1A MLH1 TWNK PIGN GABBR2 EYA1 ZAP70 TP63 TPRKB BUB1 CYP7B1 POLR3A SFTPA1 TTBK2 SPG21 CARMIL2 ACTA1 RTEL1 PROKR2 EWSR1 SLCO1B3 DPYS ASXL1 TNPO3 TGFBR2 MECP2 REPS1 ERCC4 SLC46A1 NOTCH1 TSC2 ABCC6 BAX FAN1 QDPR ZNF423 TRIP4 BMPR1A NDUFAF2 ARHGAP29 VPS33A NOTCH2 MLH1 FOXP3 DACT1 CRYAB TWNK DYSF CACNA1A KLLN ENG ELANE PLXND1 INPP5E YARS2 SYT1 LMX1B EDNRB ATXN2 WAS USP27X PIGT DHCR7 TK2 FBN2 PIEZO2 TP63 RASGRP1 PSPH POGZ CIITA PSEN1 NRXN1 FGG PNKD TMEM237 NEFH BMPR1A CACNA1A POU2AF1 EHMT1 COX4I2 KIF1A MYPN MLH3 NOTCH3 RPL10 DACT1 TSPYL1 SLC25A13 TP53 PQBP1 FRG1 FOXG1 ITGB4 RARB CEP290 FOXC1 GRIP1 VAMP1 SRP54 GLI2 ORC4 NOP56 WDR73 C19ORF12 CD79B KAT6B EBF3 SPG21 RAD51 AAGAB PACS1 SRSF2 TP53RK IDH1 KRAS CHEK2 RET PPP3CA F9 FBXL4 TP53 WHCR COL1A1 KLHL40 HMBS HCCS MSH2 SLC5A7 ARF1 CLMP AP1S1 LMNB1 NOTCH2 FERMT1 GLRA1 VAC14 ITGB2 MSX1 VCP MCM6 PIK3R1 PEX16 USF3 NOP10 DNAJC21 SCN9A MTTP LIPA CCNQ TNFSF12 STUB1 ACTA1 GMPPA SDHA USP9X NHP2 SLC35A2 NBN CAMTA1 PEX3 PYROXD1 CD109 HPGD EIF2AK3 ENG SKI CASP8 GATA6 UBA5 SIK1 USP9X MBTPS2 PHOX2B TPM3 APC MAP1B DKC1 ERLIN2 WDR73 PITX2 FGFR1 ARID2 SYT14 JAK2 EPCAM KMT2D SLC6A8 CLCN4 NEB F7 KRAS FMR1 BLNK POMT1 BACH2 GBA SLC13A5 ARID1B STK11 STAT3 SPINK1 TCF4 GPC3 MEFV NEB CTLA4 SACS BRIP1 ATRX TYMP TTC37 SALL4 SMO IGH CHD7 STN1 PEX1 NFIX ND4 GPC3 MLH3 FAH MSH2 POLG2 CCND1 MSH3 NCAPG2 ATP7A MCEE STX3 MEGF10 ATP1A3 GIGYF2 COLQ TCF4 RUNX1 TRNK ORC6 DCLRE1C HRAS FGA SETBP1 RAI1 SLC35A2 SLC37A4 TFAP2A PTCH1 SEMA3E CHST14 CEP120 IL1RN INPP5E MUTYH PALB2 PEX10 STUB1 NUP107 COL7A1 CACNA1B WRN TRAPPC12 CD3G BRAF IL10RB POU6F2 RAD21 F12 DAXX C4A MNX1 GREB1L FLCN TPM2 RPS6KA3 EXOSC9 LRP12 CTNNB1 FANCA KLHL7 WFS1 MST1 PEX12 DSE NCF4 KRAS SLC2A2 VARS1 GEMIN4 TCTN1 NECTIN1 UROD ALDH18A1 F5 TAF1 XRCC2 TTC7A WFS1 ASCL1 IL1B TERF2IP NTNG1 TRAPPC11 FGFR2 OCRL ZSWIM6 SUZ12 ARL13B ERCC2 AGPAT2 TINF2 KCNB1 HSD3B7 ATP11A TAF1 CEP104 UBQLN2 GTF2IRD1 ND5 MUC5B FANCB FAS RAD21 NPC1 MYH3 GPIHBP1 SCN4A COL18A1 CEP57 PSAP SMARCD1 BAP1 FANCM FGA PLEC AGRN POLG ACTA1 GPC4 MACF1 SNCAIP PRKCG XRCC4 TET2 DIS3L2 TGFB1 ARMC9 SDHB MAP2K2 NCF1 PIK3CA CHMP2B CLIP2 COG6 COMT POR XYLT1 STAT4 GP1BA HLA-DRB1 GLIS3 PLAA ERAP1 MAFB TRMT5 SOX5 APC PCGF2 ENPP1 NOTCH1 PPP2R5D HIRA DKC1 TGFBR2 DKK1 MSH6 RNF125 TGFBR2 PTDSS1 CPLX1 WFS1 PMS1 VWF MMP1 SEC23B TJP2 DYNC2I2 ZNF41 TEK CHRM3 PCSK1 RERE STX1A IRF2BPL PLA2G2A RNF43 HLA-B POLG RMRP FGG WNT3 MKS1 BRCA2 IL2RB LMNB1 TRNL1 KCNK9 SIX6 GREM1 PARN PAX4 ACOX2 MEFV PRKRA C11ORF95 SYP SDHB PACS1 PLAGL1 GLRB NDUFS1 KCNC3 HNF1A RFXANK ND3 SEMA3C SLC9A7 SOX10 ND6 MED12 RPS20 FGFR2 KMT2A AGA NOTCH3 FGF12 ACTG2 PIBF1 NCF1 CR2 IL2RA MYC SLC7A7 CAVIN1 TIMM8A KCNQ1 NFKB2 EIF4G1 DLX4 IFNGR1 KCNA2 NBN GCK FREM1 ALG8 CTC1 DNM1L FGFR2 SRC RET CDKN2B SMAD3 TRNL1 POLR3A HDAC8 TUBB6 THOC6 FGFR1 DCTN1 CHEK2 PIK3CA DHCR7 CHRNA1 SCN3A AMACR ATXN10 NAB2 NDUFB8 SLC1A4 RECQL4 NGLY1 PEX16 RAD51C MITF SNAI2 SALL4 SETBP1 ATRX REEP1 SLCO2A1 PHOX2B PDGFRA SDHD LAMA3 ZIC3 B3GLCT RAI1 SALL1 HCFC1 CDKN1B AXIN2 COX7B NEUROD2 NEUROG3 DSP VAC14 NHP2 SDHC CBLIF ND1 GALC MSH2 ALDH18A1 KCNK9 PLA2G4A ARFGEF2 TRNE ND1 UBE3B MKKS EDN3 GP9 F5 IL21 CDH1 TNFRSF13C HLA-DRB1 FOXE1 TBCE FLNA ADAR GJB2 MAP3K7 PHOX2B POLR3B TGFBR2 AFG3L2 MED17 MECP2 GDNF FXN SMPD1 FANCB PKD1 FANCD2 LARGE1 ZIC3 BIN1 SLC39A4 POLG PMP22 ABCB4 DVL3 PLCG2 DMPK POLG2 GBA2 TWIST2 CHEK2 DGUOK BAZ1B EXTL3 CYP7B1 TRNS2 POLE KRT8 FGFR2 POT1 EDN3 SIN3A LRP5 SYNJ1 FREM1 PIGO POMT2 MPL CDKN1A ACTB CFTR CFC1 UBTF NONO CACNA1G ITGB3 GRIN2D MYH7 EFL1 CAVIN1 KLF6 DLG1 PIGA TYROBP TREM2 JAG1 KIT SOX10 FAH CEP41 NONO CDK8 SAR1B STAT1 SCN4A TARDBP ATAD1 PAX3 FGFR3 SLC10A2 PTEN MEN1 TPM3 IL12B IRX5 NPHS1 NTHL1 SLC30A10 NDUFA6 SEC23A AIRE LMOD3 SF3B4 CDCA7 NECTIN1 L1CAM PRPS1 PIGV NDUFS3 FMR1 FH KLHL40 POLE SMC1A ALG13 RFX5 KAT6B AKT1 AAAS PMS1 GBA PUF60 BTNL2 SPART CDKN2A PGM3 NOS1 TBC1D24 PAX3 CTRC FLII FRMPD4 MAP3K7 MC1R MYOD1 IL10RA BBS1 AXIN2 NDUFA9 EP300 GLI3 CCN2 ECE1 EOGT CHAT EDNRB SERPINH1 HMBS CTCF OPTN FOXF1 GP1BB F8 CXCR4 TRNK MASP2 IRGM GATA6 GABRD RET TBCD AFG3L2 COG4 ATXN7 CSPP1 ATRX MUSK RET MPI MEN1 GABRA5 ATXN1 TNFSF12 C12ORF65 SPINK5 CCR6 IL6 TXN2 PDGFRL SNRPB ALS2 APC HYLS1 MCOLN1 PRKCD KCND3 RPS19 LAGE3 TRAPPC11 SUFU PLAA IRF6 ZNF81 LIPA SETX DOCK8 CCDC47 DNAJC13 STS GPHN FANCL FGF20 ATXN8OS DDX59 FOXG1 KLF11 COG7 IL12A-AS1 CNKSR2 SLC6A19 FOXH1 STAG1 RELA MLX SLC1A2 FGFR2 SYT14 LCT TJP2 PORCN CD81 PNP PRPH WRAP53 SMC1A RAB39B MYRF DLC1 CTNNB1 WNT2B MAPT CLCA4 CLCN1 ITGB3 SERPING1 PCNA CDK4 FKTN ITGA6 AKT1 LRBA BAAT VAPB PRKCSH DDX59 KLRC4 PIEZO2 TGM6 PEX6 DDIT3 ACVRL1 WDR26 EP300 PALLD HLA-B DCHS1 RET CTLA4 SHANK3 B3GALT6 SCO2 NDUFS2 CACNA1G POLG HSPA9 HSD3B7 TP53 FLI1 GYS2 MAN2B1 GPC4 RAD21 PMS2 ASCC1 HLA-DQA1 GAS1 FASLG COX3 FANCB DNAJB6 SMAD4 FTL KIAA0319L COQ4 ATM PIGN ARVCF MID2 KIAA0586 OPLAH INPP5E JAK2 TGIF1 ATXN1 MAPT IQSEC2 SKI SLC9A3 LAMB3 SDHC RBPJ AAAS MKKS GALC KY CISD2 B3GLCT EXT2 F5 TBP ZAP70 UBE2T AHI1 QDPR F13A1 ATP8B1 COMP SMC1A CHCHD10 PPARG GDNF STAG1 CDKN2C HLA-DQB1 CTNND1 TBC1D23 DLEC1 EFEMP2 PORCN FLCN RBM10 SPIB SLC52A2 SDHB RFC2 CDKN2A NLRC4 GABRG2 POLD1 DCC SRP54 SNAP25 TSC1 MYORG CCNQ NCF2 TNFRSF13B RNASEH1 SPINT2 CASP10 FGFR1 TERC PMPCA SZT2 MRE11 DDHD2 MYCN CHRNE JMJD1C VANGL1 AARS1 ARPC1B CEP120 JUP SPG7 OSGEP TRIP13 MSX1 SIX1 YWHAG FLNA NEK9 JAK3 NAA10 CTNNB1 IDS POLR1C SBDS ND5 ECM1 NFKBIA SLC19A3 BUB1B TIMM8A BRCA2 TCIRG1 CDH11 ELP1 MTMR14 ACTA1 ASPA MFF ATP6 RMRP TCTN3 SETD5 TK2 TRNW SOX2 PTCH2 TBX1 CCBE1 CDH1 HNF4A SLC52A3 HPCA JAK2 ASCC1 TNXB DHDDS CLCN4 GMPPA GNAS NGLY1 SEC24C DYNC2H1 ALDH18A1 MAGEL2 MECP2 MUTYH HCN1 SYT2 LAMB2 COL7A1 MSR1 TRMT10C RB1 SLC25A4 SYNGAP1 ISL1 GPC3 PGAP2 MEIS2 NUP88 RSPO2 ACD FANCE CYBA SHANK3 NPHP3 NEFH VAMP1 TMEM237 MET SCN4A SLC25A13 CHST14 SMO RFWD3 PDGFRA IGF2R POLR3A TGFB2 UPF3B SMG9 SURF1 ATP6V1A TTC7A CDON NIPBL IDH2 HNF4A CHD4 KIFBP MATR3 HFE GNS BRIP1 NPHP1 PEX5 ACVRL1 RRM2B FLCN GDF3 ABCB11 ATXN3 ADNP HNF1B EXOC6B LONP1 PEX26 TRIP13 SEC23B HTT SALL4 BRCA2 ITGA2B CHRND JAK3 FIG4 SMC3 GDNF NALCN ACOX1 LINGO1 RFXAP RHBDF2 TTC37 FARSB NPC2 RERE SQSTM1 NRXN1 ACTA1 TMEM67 TAF1 LAMA3 KRAS MLXIPL KCNJ11 ALS2 RNASEH1 FREM2 SALL1 ATP6 CYP27A1 PEX12 FREM1 IKZF1 UBAC2 PAK1 POLG ABCC2 PRKRA SSR4 SLC2A10 MAP2K1 CHN1 DNMT3B CEP120 GJB6 AK2 CHAT FGB SERPING1 TP63 NDUFB11 HLA-DPA1 LRRC8A SHPK ABCC8 AP3B2 TLR4 SLC25A13 TCF4 MYOT PANK2 SHROOM4 STXBP1 DMP1 NUS1 PTEN RAPSN LBR TANGO2 ITGB4 PANK2 WNT3 MLH1 MATR3 PKHD1 SNCA EDNRB CRLF1 GRIN2D GATA1 BMPR1A PANK2 WNT7A GTF2I MID1 KLHL41 MVK GDF2 KIF23 FLNA PTEN MCC NUP214 STXBP1 EPCAM KBTBD13 ATP13A2 LAMB3 IL10 FLNA SHH NPM1 SLC37A4 DDOST SH2B1 IARS2 INHBA SLCO1B1 DNAJC21 SKIV2L NF1 SOX10 TBK1 VPS13A ARV1 ASAH1 AGTR2 HLA-B WT1 SLC6A3 GNA11 COL5A1 MPZ BARD1 PTPN22 CYBA TRNW COL7A1 EDN3 AFF4 ARX ATXN8 PTPN3 TERC ABCD4 ORC1 HPS1 WASHC5 TP53 NEXMIF CYP27A1 ARNT2 HNRNPU BUB1B NCF2 FIG4 DLG3 FANCC ITGB3 GABRB2 DLL4 GUCY1A1 RAD54B TBL2 OTX2 SDHB NOD2 TMPRSS6 RBM8A CDKN1B IGF2 BMP4 CEL RFX6 SETX TCF3 ND2 CYBB GP9 ACTG2 FBN1 TNXB DAB1 SUFU BTK ELN CD55 HYMAI FLVCR1 PHOX2B STAC3 USB1 FLNB HMGA2 SMAD4 PLA2G6 PGAP3 RFX5 AMACR KLHL41 SMAD7 MKS1 MCFD2 POLA1 F13B SLC30A2 COL3A1 CD96 GLUD2
Protein Mutations 2
C10D V30M
HP:0001638: Cardiomyopathy
Genes 730
NDUFS1 LIMK1 LIPT1 TTR MPLKIP MICOS13 INSR NEB CPT2 TNNT2 PSEN1 FKRP LMNA KCNAB2 MYH7 SGSH FANCL EPB42 LAMP2 CSRP3 SLC22A5 TSFM LMNA ND2 TNNI3 RAF1 GPC3 PEX7 ELN NDUFS8 EYA4 TNNI3 PDGFRA MLX BRIP1 PCCB GMPPB KRAS ECHS1 TPI1 NDUFS7 NDUFAF1 NDUFV2 GBE1 RRM2B BOLA3 MRPS14 SMC1A SYNE2 MRPL44 HAMP TRNT1 LIMS2 NRAS SHOC2 DOLK HCCS HADH DMD GLA ND4 TMEM43 NDUFS3 DMD PET100 NDUFV2 TNNT2 RAF1 NDUFAF2 LMNA FHL1 SHOC2 AGK HSD17B10 TNNI3 TRNQ TRNK SDHB XYLT2 TTPA AGK HRAS SCO2 NDUFS2 FHL2 NDUFB11 RNF113A TNNT2 MYBPC3 SYNE1 MRAP TRNT XRCC4 ACTN2 VPS33A DLD BSCL2 BBS2 KCNH1 CRYAB PHYH MYSM1 SLX4 PCCA VCL AGL GPC4 TOP3A INSR TIMMDC1 NDUFAF8 NDUFB10 TMEM70 COX3 LMNA LMNA ACADVL SARDH COX8A BRAF TREX1 DES SLC19A2 LMNA HGSNAT MLYCD PEX1 COQ4 DES TPM2 SLC25A20 TCAP LAMA4 FANCA DMD WFS1 ATP5F1D LAMA2 TMPO NDUFS6 TNNT2 ARSB TNNC1 FOXRED1 NDUFV1 PTPN11 FKTN NBAS DMD SKI LAMB3 NDUFA11 LAMP2 SLC25A4 SELENON FOXRED1 XRCC2 UBR1 NDUFAF4 LMNA FOS CISD2 JPH2 HFE RBM20 MMP1 GNPTAB RNASEH2B LDB3 GMPPB IGF2 PPARG UBE2T SDHA FKRP PRKAG2 SLC25A4 AGPAT2 DSP PPA2 TNNI3 ATAD3A CLN3 PLN TRNS1 GNE ANK1 PMM2 TPM1 GTF2IRD1 ND5 PEX16 TPM1 PPARG TWNK HADHA TRNH NDUFS8 SDHD NDUFAF3 FANCB PEX11B LIAS TMEM126B MYOZ2 HNRNPA2B1 SLC19A3 PCCB DPM3 STAR SGCB PEX5 NDUFS2 MYH7 MYLK2 GSN FANCM RFC2 ERCC4 SDHAF1 MYPN HAND2 POLG ACTA1 COX6B1 PCCA MEN1 PEX12 RAF1 GPC4 CRYAB RAF1 COX14 FHL1 GATAD1 NDUFA12 RYR2 MYH6 TMEM43 POMGNT1 NEBL ANKRD11 NEB NDUFS8 ITPA POMT1 MAP2K2 PTPN11 TAF1A ACTC1 RBM20 CLIP2 PYGM XYLT1 FKTN POMK COA5 XK ALG1 DPM3 MIB1 GLB1 COA3 SCN5A TMEM70 ERCC3 NDUFS2 ENPP1 NDUFV1 JUP NEU1 MGME1 GTPBP3 DMPK CAP2 TNNC1 ADAR CHKB BRCA2 PEX19 LAMC2 IFIH1 COX1 MRPL3 WFS1 AIP TMEM126B MYPN MYL2 DSC2 ND5 HBB BRCA1 FKTN SCO2 MYH6 TPM3 MYH7 IDUA GSN ND6 EPG5 PTPN11 RRM2B SDHD POLG TARS1 POMT2 ALMS1 FLNC BMP2 COX15 TRNL1 HJV HMGCL DMD MAD2L2 ACTA1 RYR1 TERT AHCY GATA4 NUP107 NDUFAF2 COX15 KCNQ1OT1 SLC25A3 NDUFA10 BCS1L TRNL1 RNU4ATAC RMRP POMT1 SLC4A1 LTBP4 TANGO2 NDUFA10 ACAD8 BRAF ND3 CAV1 MYPN RNASEH2C ABCC9 CPT2 TK2 TRNW MTFMT CPT1A NDUFB3 ND6 CDKN1C NDUFA2 TKFC ABCC6 SUFU PIGT COX2 NDUFAF3 COX20 PYGL MYH7 ACTN2 ACAD9 ADCY5 USP9X CSRP3 NDUFA4 SGCD BSCL2 KCNQ1 DOLK TPM3 MGME1 TPM2 RAF1 DSG2 BAG3 SOS1 H19-ICR HAMP TAPT1 FTO ACTC1 NDUFA9 HADHB MAP2K1 DSP ERBB3 COL7A1 PMM2 SLC25A4 FLNC TGFB3 TNNI3 TRNL1 POMT1 PRKAG2 COL7A1 MTO1 PALB2 GPC3 NDUFS7 FKRP AARS2 FANCE RNU4ATAC TNNT2 SCO1 TRIP4 ADCY5 PRDM16 NDUFAF6 NDUFAF5 PPP1CB HNRNPA1 MYO18B SPTB PGM1 GATA5 NDUFB8 LAMA4 FKTN ANKRD1 DTNA RFWD3 KRAS ELAC2 ABCC6 TACO1 MYBPC3 TRNF ALMS1 TAZ PARS2 SGCA CPT2 NDUFA13 ND3 SURF1 TCAP HADHA COG7 COX7B CPT2 PET100 LAMA3 GTF2H5 GMPPB MYOT PRDM16 MRPS22 TXNRD2 COX7B PHYH GYS1 CENPE HADH PEX26 HFE COQ2 GNS NPPA ND1 SLC25A20 ATPAF2 KLHL41 DCAF8 WARS2 TTN PSEN2 TPM1 TRNE ND1 GATAD1 SYNE2 SELENON FANCF SAMHD1 NAXD COX10 PEX7 C1QBP VCL GPR101 PEX3 NAGA PRDM16 MMUT RAB3GAP2 EYA4 DES FIG4 GTF2E2 NDUFS1 IDH2 SGCB JUP TNNC1 FANCG RERE PSEN1 PKP2 TNNI3 NAGLU COA8 KRAS SDHA AIP TAZ NDUFAF5 RNASEH1 ATP6 FXN NUP107 HLA-B FANCI KAT6B ACADL TWNK HADHA PEX13 FANCD2 POLG TPM2 SDHAF1 ABCC9 MYH7 MYH6 PNPLA2 POLG ACTA1 MYH7 SLC2A10 GTPBP3 TFR2 DSG2 MAP2K1 TWNK POLG2 MYL3 BAZ1B FLAD1 TRNS2 ND1 NDUFS4 FLNC ABHD5 HACD1 TXNRD2 PPCS ITGA7 NDUFB11 SDHA TRNK PEX2 TRNN NEK8 PPCS ACAD9 PLN DSG2 COA8 MYH7 CLPB RMND1 CAVIN1 MIPEP DSP MYOT NDUFAF4 COA6 TMEM126A RAD51 VPS33A LDB3 TAZ TTN TACO1 CRYAB TWNK MMUT ANO5 SLC25A4 RIT1 BAG3 FAH TTR ACADS IDUA YARS2 TRNS1 SDHA RBCK1 GTF2I EMD MAP2K1 ANKS6 EPG5 HRAS PIGT HADHB MC2R MAP2K2 CRYAB NDUFV2 MYBPC3 KBTBD13 TPM3 PSEN2 GNPTAB HJV BRAF IL12B SPEG PEX6 SLC30A10 NAGA GJA5 NDUFA6 SURF1 SCN5A D2HGDH UQCRFS1 NF1 LMNA MYPN VPS13A ATAD3A NNT RAD51C ACTC1 TKFC LMNA CDH23 NDUFS4 DNAJC19 TNNI3K LMNA NDUFA2 KLF1 JUP BRAF KCNJ8 TRNW TTN ALG1 LDB3 NDUFA1 ERCC2 GYG1 PDHA1 NDUFA11 LMNA HPS1 SDHA AIP LDB3 CAV3 MYL2 SGCD ATP6 NEXN CSRP3 NDUFAF1 NDUFS3 FIG4 NDUFS2 FANCC ND4 NDUFS4 FBXL4 DNAJC19 OPA1 PLN SLC40A1 ATP6V1A PEX10 TBL2 FHL1 PEX14 PRKAG2 HCCS SPTA1 DLD AHCY VCL DES SLC25A3 VCP ACADVL TRNK DSP MYPN PEX7 GABRD ABCC9 VAC14 ND2 FHL1 AGPAT2 FOXRED1 ATP5F1E POLG HADHA NDUFB9 ACTA1 RNASEH2A KIF20A DSP FXN TRNV POMT2 NDUFB11 JUP TTN IDUA NDUFB11 ACAD8 NEXN MAP3K20 MYH6 PNPLA2 POMT1 TGFB1 NEXN USP8 GUSB BAG3 NUBPL
SNP 0