SNPMiner Trials by Shray Alag

L858R (324) T790M (316) V600E (256) T315I (102) L861Q (92) M184V (67) V617F (54) G20210A (53) K65R (52) V600K (51) C282Y (50) V66M (49) G551D (42) P13K (39) C677T (34) A118G (29) I84V (27) V158M (26) H63D (25) V32I (24) S768I (24) I50V (23) I47V (21) K103N (21) Y181C (20) L33F (19) K27M (19) T380A (18) L76V (18) D842V (18) D816V (17) S1251N (17) S1255P (17) G178R (17) G1244E (17) S549R (17) G1349D (17) V82A (16) R117H (16) M41L (16) S549N (16) G12C (16) C3435T (16) G551S (16) Q151M (16) Q12H (15) K219Q (15) I54L (15) G719A (14) K70E (14) C797S (14) L90M (13) L74V (13) E138A (13) D67N (13) K70R (13) L89V (13) L210W (13) Y188L (13) P4503A (12) G11778A (12) L265P (12) M46I (12) I54M (12) G12D (12) V11I (12) R132H (12) G48V (11) D961H (11) T74P (11) R192G (11) E255K (11) V299L (10) K101E (10) G2677T (9) T25W (9) V106A (9) G12V (9) M184I (9) H221Y (9) V30M (9) V600D (9) G1691A (8) F227C (8) T215Y (8) I50L (8) A1298C (8) L100I (8) Y253H (8) F317L (7) N155H (7) S298P (7) G190A (7) M230I (7) C1236T (7) V600R (7) Y188C (7) G2019S (7) P225H (6) Y93H (6) F359C (6) V108I (6) A3243G (6) G73S (6) P12A (6) Y115F (6) E545K (6) Q148H (6) Y537S (6) E542K (6) I10A (6) M230L (6) H1047R (6) N40D (6) D299G (6) D30N (6) M235T (6) D538G (6) Q12W (5) I148M (5) T87Q (5) I47A (5) L74I (5) E92Q (5) N680S (5) G93A (5) A455E (5) M204V (5) D1152H (5) L755S (5) G13D (5) G190S (5) N363S (5) A181V (5) V179L (5) L24I (5) N88S (5) A2143G (5) T399I (5) M36I (5) F53L (5) T315A (5) R263K (5) R132C (5) V777L (5) T1405N (4) D579G (4) G719C (4) N370S (4) R117C (4) Q16W (4) L98H (4) A98G (4) K20M (4) E138G (4) E138K (4) L31M (4) E157Q (4) L10F (4) Q80K (4) C31G (4) L206W (4) P140K (4) I54V (4) K76T (4) Y537C (4) I1314L (4) S945L (4) Y402H (4) P1446A (4) V179D (4) N88D (4) A6986G (4) N236T (4) A1166C (4) G970R (4) Y181I (4) R352Q (4) G2385R (4) S310F (4) P67L (4) R1070W (4) G140A (4) E23K (4) S463P (4) T14484C (3) G719S (3) R206H (3) S1400A (3) S1400I (3) A71V (3) C134W (3) R24W (3) C481S (3) T24H (3) V122I (3) T47D (3) A636P (3) S977F (3) G118R (3) G3460A (3) N312S (3) G1202R (3) D988Y (3) Q252H (3) L444P (3) V659E (3) V769L (3) A147T (3) E10A (3) L861R (3) R678Q (3) Q27E (3) E17K (3) Q148R (3) A1555G (3) S49G (3) Y537N (3) R16G (3) I10E (3) V158F (3) G21210A (3) K55R (3) V205C (3) Y181V (3) A2142G (3) R506Q (3) E298D (3) L211A (3) R172K (3) V843I (3) Y143R (3) R572Y (3) G143E (3) G1321A (3) V842I (3) H295R (3) G140S (3) T60A (3) P23H (3) F11N (2) S1009A (2) H275Y (2) T733I (2) F1074L (2) I1307K (2) G250E (2) S77Y (2) E28A (2) E28C (2) E28D (2) T66A (2) S1400C (2) S1400E (2) S1400D (2) D1790G (2) L833F (2) S1400G (2) S1400F (2) R334W (2) L8585R (2) I105V (2) N375S (2) V560G (2) T20S (2) T69D (2) T69S (2) Y93C (2) E138R (2) E138Q (2) F359V (2) R776H (2) Q422H (2) D110H (2) D110E (2) R753Q (2) R404C (2) C283Y (2) L31F (2) S252W (2) L460D (2) L33I (2) R140W (2) R140L (2) R140Q (2) V106I (2) V106M (2) E709K (2) P50I (2) V697L (2) P535H (2) P51S (2) G1314A (2) S492R (2) G308A (2) G71R (2) T215F (2) E56K (2) A2063G (2) D769H (2) L248V (2) E280A (2) Q21D (2) E504K (2) Q141K (2) R496H (2) S100P (2) L536R (2) L536Q (2) L536P (2) A143T (2) C19P (2) T97A (2) G3556C (2) Q24W (2) K751Q (2) T4396G (2) V151L (2) G170R (2) A581G (2) L536H (2) G12R (2) G193E (2) F876L (2) R479H (2) Q28D (2) G190E (2) R347H (2) K601E (2) G16R (2) R831C (2) G5271C (2) V75I (2) G681A (2) A270S (2) L63P (2) L869R (2) P236L (2) R831H (2) T13D (2) H1047L (2) C3670T (2) V34L (2) E255V (2) G469A (2) V57I (2) L144F (2) M233I (2) C825T (2) C8092A (2) G776C (2) G776V (2) F121Y (2) R172S (2) R172W (2) R172M (2) Q192R (2) R172G (2) E380Q (2) Y121F (2) K101P (2) R61C (2) V600M (2) F31I (2) K540E (2) K103H (2) R132V (2) D1270N (2) R1628P (2) R132S (2) V534E (2) R132G (2) R132L (2) K238N (2) G4655A (2) S112A (2) I84A (2) Y129S (1) G1388A (1) S77F (1) R20A (1) V140A (1) C686A (1) I1768V (1) E25K (1) K652E (1) C420R (1) S9304A (1) R337H (1) C421A (1) V189I (1) K304E (1) A7445G (1) D19H (1) L304P (1) Q36W (1) Y454S (1) A133S (1) M9T (1) P596L (1) E318D (1) C1156Y (1) N171K (1) A7445C (1) V82F (1) G47A (1) R447H (1) G47E (1) V82L (1) R776C (1) A92T (1) E27Q (1) F1052V (1) P27A (1) A289T (1) L523S (1) H54Y (1) T1095C (1) S428F (1) R400C (1) D313Y (1) Q12M (1) R139C (1) A393T (1) W719R (1) T66K (1) T862I (1) T66I (1) G49A (1) R48G (1) H58C (1) I104F (1) D203E (1) K656E (1) T40S (1) D312N (1) G276T (1) L747P (1) R200W (1) L747S (1) I1171N (1) Q14D (1) S1400K (1) R115G (1) F17L (1) A71T (1) S339F (1) A71L (1) F317V (1) F317S (1) G20201A (1) F317C (1) G2545R (1) C377T (1) S9346A (1) P243R (1) R25L (1) L528M (1) Q222R (1) I22M (1) I107M (1) C1858T (1) L859R (1) G2032R (1) A859S (1) G389D (1) V148I (1) K65E (1) V148G (1) C242T (1) G389R (1) H369P (1) A98S (1) G2500A (1) I349V (1) I107V (1) V561D (1) C481R (1) L833V (1) P200T (1) G1051A (1) Y93F (1) Y414C (1) Y1248H (1) K65N (1) L74M (1) P4502C (1) Y1248C (1) Y1248D (1) F227R (1) V89L (1) T164I (1) G1628A (1) A2215D (1) C94A (1) H1124D (1) E200K (1) F227L (1) I305F (1) N682S (1) T1010I (1) I655V (1) R885H (1) G7444A (1) R776G (1) E354Q (1) A21443C (1) R620W (1) A54T (1) D594G (1) T49A (1) F116Y (1) H870R (1) G205S (1) R535H (1) I767M (1) L55M (1) E571K (1) L55R (1) M2540A (1) E92K (1) G238A (1) L838P (1) E6V (1) L814P (1) K509I (1) V21I (1) G699A (1) V167F (1) L33P (1) M66V (1) D61804R (1) R849W (1) V762A (1) D816H (1) V326L (1) V108M (1) L58H (1) V411L (1) E158K (1) N334K (1) A1067T (1) S1800A (1) G894T (1) G202A (1) C282T (1) I191V (1) G435A (1) K1060T (1) A10H (1) R272G (1) V654A (1) V106T (1) C1091T (1) I638F (1) P317R (1) V433M (1) S230R (1) R4E (1) N550H (1) P1058A (1) N550K (1) E709Q (1) G304A (1) T124A (1) S253N (1) G1316A (1) M552V (1) M552I (1) R182H (1) D835V (1) A871E (1) D835Y (1) A677G (1) C1950G (1) H1505R (1) A893S (1) L597Q (1) S2808A (1) N55H (1) K28M (1) D89E (1) L485W (1) M9346A (1) L159F (1) A437G (1) R92Q (1) V29C (1) L38V (1) G135C (1) A677V (1) C34T (1) G93R (1) R270H (1) V321A (1) C10D (1) R122W (1) G308V (1) H2507Q (1) D20W (1) G309A (1) G309E (1) G721A (1) I90P (1) C59R (1) C416R (1) G71A (1) Q61R (1) Q61L (1) H835L (1) R498L (1) V941L (1) Q62E (1) R389G (1) D769N (1) G156A (1) E1784K (1) G98T (1) Q65E (1) T92A (1) S239D (1) C656G (1) R451C (1) G73C (1) G5665T (1) R72P (1) F64L (1) L248R (1) M204I (1) R149S (1) A105G (1) M28L (1) D769Y (1) V769M (1) R75T (1) E193K (1) T890M (1) P250R (1) P58A (1) L532S (1) S147G (1) S1235R (1) T454A (1) K660E (1) R76K (1) L1213V (1) V742I (1) V1238I (1) R74W (1) T102C (1) K3048A (1) T93M (1) D961S (1) G1269A (1) R277W (1) P187S (1) A561P (1) Q20W (1) V740A (1) T783I (1) T674I (1) S8814A (1) T783A (1) V90I (1) C325G (1) Q188R (1) R30H (1) C785T (1) S100A (1) R496L (1) G174S (1) P11A (1) L798F (1) V765A (1) G1049R (1) C18S (1) L798H (1) V765M (1) R230C (1) S366T (1) G1376T (1) S65D (1) A277G (1) T1191I (1) L755A (1) T878A (1) H131R (1) T854A (1) P253R (1) C1494T (1) L755P (1) P120H (1) E525K (1) C102T (1) Y1253D (1) G196A (1) K70N (1) A145T (1) L861G (1) H43R (1) I76V (1) C344T (1) R677W (1) S9313A (1) F1174V (1) I112T (1) G10V (1) R10C (1) F1174L (1) R10A (1) K860I (1) R34P (1) F1174C (1) R108K (1) I112M (1) I332E (1) V151I (1) S1369A (1) R32Q (1) N409S (1) C563T (1) Q24H (1) I113T (1) D761Y (1) Y114C (1) N291S (1) G34A (1) G1069R (1) V151A (1) R896C (1) S567L (1) A827G (1) G12S (1) I54T (1) D565H (1) Y113H (1) P367L (1) R102G (1) R368H (1) M3002A (1) P125A (1) V282M (1) E545G (1) M1040E (1) E545A (1) G398A (1) E545D (1) L409P (1) S1787N (1) G12A (1) S784P (1) L841V (1) R14C (1) S9333A (1) V943A (1) Q148K (1) Q148E (1) M1043I (1) Y220C (1) T416P (1) A3669G (1) R38H (1) T961C (1) T961G (1) L84F (1) V1110L (1) E326K (1) S108N (1) C365Y (1) A719G (1) D237E (1) G37R (1) D104N (1) S653C (1) S786I (1) V834I (1) Y376C (1) G3514C (1) G594A (1) G1947A (1) G190C (1) V834L (1) Q546R (1) F522C (1) Q546L (1) Q546K (1) P699S (1) F2004L (1) D101H (1) T393C (1) A1330T (1) R988C (1) H48Q (1) T174M (1) A62V (1) A62T (1) L84V (1) M165I (1) V222A (1) P479L (1) Y318F (1) G908R (1) V75M (1) D101Y (1) I10F (1) D90V (1) H1112L (1) V30A (1) R3500Q (1) S282R (1) D919G (1) I665V (1) H1112Y (1) D90A (1) C385A (1) M95L (1) G1170S (1) V244M (1) G17T (1) S26E (1) N251K (1) G464V (1) C807T (1) V77I (1) Y449D (1) D4064A (1) C168H (1) Q215S (1) M50I (1) K56M (1) F106C (1) G465R (1) G598V (1) S769N (1) E586K (1) T1482I (1) L1196M (1) E148Q (1) T12W (1) S720P (1) Y641S (1) S768R (1) F129L (1) Y641N (1) C938A (1) C165V (1) R19C (1) C383R (1) Y641H (1) Y641F (1) C805S (1) W64R (1) Y641C (1) H1047Y (1) M1268T (1) A736V (1) C61G (1) P1009S (1) V481F (1) S1612C (1) Q546E (1) L718P (1) V179F (1) M1002A (1) G106R (1) P300D (1) S131F (1) W21C (1) L144S (1) M1149T (1) H558R (1) S373C (1) A69S (1) V774A (1) T377M (1) V689M (1) V774M (1) D164V (1) R199W (1) N86S (1) N86Y (1) G11053T (1) R175H (1) T17M (1) Y86N (1) A2144G (1) N345K (1) A2059G (1) D50W (1) I180V (1) A864V (1) L24E (1) V118I (1) G212S (1) I843S (1) N1303K (1) R1623Q (1) A1033V (1) L1198F (1) N1325S (1) V773M (1) Q812R (1) G212A (1) A997T (1) S241T (1) E167K (1) G1764A (1) G80A (1) E62D (1) E274Q (1) M34T (1) G401S (1) A2142C (1) G211A (1) D76Y (1) G1631D (1) D76N (1) E384G (1) V249I (1) M1106C (1) L234I (1) A2143C (1) L101I (1) K806E (1) A687V (1) A119S (1) P1028S (1) A313G (1) D824V (1) S9C (1) C182A (1) S9G (1) S153F (1) S1900D (1) S1900C (1) R1644H (1) S1900A (1) T1456G (1) R702W (1) T1565C (1) E1021K (1) K15210D (1) G82S (1) G779C (1) G840A (1) G779F (1) V18M (1) A27L (1) L28M (1) T351I (1) K121Q (1) H180Q (1) L28P (1) G779S (1) M11T (1) M11Q (1) P549S (1) N215S (1) R352W (1) G60D (1) G84E (1) E161K (1) G951A (1) C23S (1) E184K (1) V1206L (1) Y842C (1) L432V (1) V736A (1) E89Q (1) R135W (1) Y253F (1) G843D (1) D820Y (1) F77L (1) S311C (1) D10W (1) G86R (1) Y143H (1) Y143C (1) R112H (1) Y143A (1) A227G (1) K101Q (1) R463C (1) G85E (1) L236P (1) A310V (1) T798M (1) S310Y (1) R222C (1) A4917G (1) T798I (1) E44D (1) L302P (1) Q30R (1) L786V (1) R287Q (1) P286R (1) D36Y (1) R263Q (1) T599I (1) K103M (1) S680N (1) K1270A (1) R88Q (1) T224M (1) A5147S (1) P46L (1) N700D (1) E21G (1) Y822D (1) Q260A (1) Y188H (1) R131H (1) T81C (1) C316N (1) R1070Q (1) T1304M (1) I167V (1) I82A (1) Q54H (1) D13H (1) Q30H (1) L239R (1) Y823D (1) T117S (1) I84T (1) L106V (1) A222V (1) K432Q (1) G163S (1) I1370K (1) G163E (1) K650E (1) E757A (1) R399Q (1) G41S (1) P392L (1) C1895T (1) T334G (1) H274Y (1) R399G (1)

SNPMiner SNPMiner Trials (Home Page)


Report for Mutation R334W

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 2 clinical trials

Clinical Trials


1 Rare CFTR Mutation Cell Collection Protocol (RARE)

Over 1,900 mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein are implicated in causing Cystic Fibrosis (CF). Potential therapies that directly target defective CFTR are being evaluated in important clinical trials, but most target the most common CFTR mutation F508del. Many patients with rare CF mutations are not able to participate in those studies. The RARE study is specifically designed for people with CF caused by rare mutations. Eligible rare mutations are listed below: - CF patients who are homozygous for pre-mature stop codons - CF patients with two mutations in the CFTR gene: i. One allele must be a F508del ii. The other allele must be a pre-mature stop codon mutation - CF patients with two mutations in the CFTR gene: i. At least one allele must be a pre-mature stop codon mutation ii. The second allele can be any of the following: G85E, N1303K, R334W, 3849+10kb C->T, 621+1G->T - CF patients who are homozygous for: G85E, N1303K, R334W, 3849+10kb C->T, or 621+1G->T This is a multi-site, specimen collection study. Investigators will collect blood, intestinal cells and nasal cells from each participant. Cells from these specimens will be used to test future CFTR modulators to see if they might work for people with study eligible rare mutations. Having cells to test in the lab is an important first step in identifying potential new therapies for people with these mutations.

NCT03161808
Conditions
  1. Cystic Fibrosis
MeSH:Cystic Fibrosis

The second allele can be any of the following: G85E, N1303K, R334W, 3849+10kb C->T, 621+1G->T - CF patients who are homozygous for: G85E, N1303K, R334W, 3849+10kb C->T, or 621+1G->T This is a multi-site, specimen collection study. --- G85E --- --- N1303K --- --- R334W ---

The second allele can be any of the following: G85E, N1303K, R334W, 3849+10kb C->T, 621+1G->T - CF patients who are homozygous for: G85E, N1303K, R334W, 3849+10kb C->T, or 621+1G->T This is a multi-site, specimen collection study. --- G85E --- --- N1303K --- --- R334W --- --- G85E --- --- N1303K --- --- R334W ---

Primary Outcomes

Description: CFTR mutations will be confirmed. Once the mutations are confirmed as RARE study eligible mutations, the specimen(s) collected will be expanded, added to a specimen bank and made available to the research community for the evaluation of potential CFTR modulating agents.

Measure: The Number of samples collected from cystic fibrosis participants with rare CFTR mutations

Time: 2-5 year observational period

Description: Nasal cells will be collected from all participants.

Measure: The number of nasal cells collected

Time: 2-5 year observational period

Description: Blood samples will be collected from all participants

Measure: Number of Blood samples

Time: 2-5 year observational period

Description: Rectal biopsy samples will be collected from all participants

Measure: Number of rectal samples collected

Time: 2-5 year observational period

2 Response to CFTR-modulators in Intestinal Organoids of Patients With CF Having at Least One R334W Mutation

In contrary to what is seen in FRT cells, rectal organoids of patients with a R334W mutation do respond to CFTR modulators ivacaftor and lumacaftor. The present study will investigate the response to modulators in organoids of 30 patients with CF and a R334W mutation, to allow further stratificaton for a future clinical trial assessing the clinical effect of ivacaftor/tezacaftor in patients with CF and a R334W mutation.

NCT04254705
Conditions
  1. Cystic Fibrosis
Interventions
  1. Procedure: Rectal Biopsy
MeSH:Cystic Fibrosis

Response to CFTR-modulators in Intestinal Organoids of Patients With CF Having at Least One R334W Mutation. --- R334W ---

Organoid Study R334W In contrary to what is seen in FRT cells, rectal organoids of patients with a R334W mutation do respond to CFTR modulators ivacaftor and lumacaftor. --- R334W ---

Organoid Study R334W In contrary to what is seen in FRT cells, rectal organoids of patients with a R334W mutation do respond to CFTR modulators ivacaftor and lumacaftor. --- R334W --- --- R334W ---

The present study will investigate the response to modulators in organoids of 30 patients with CF and a R334W mutation, to allow further stratificaton for a future clinical trial assessing the clinical effect of ivacaftor/tezacaftor in patients with CF and a R334W mutation. --- R334W ---

The present study will investigate the response to modulators in organoids of 30 patients with CF and a R334W mutation, to allow further stratificaton for a future clinical trial assessing the clinical effect of ivacaftor/tezacaftor in patients with CF and a R334W mutation. --- R334W --- --- R334W ---

One or more characteristic phenotypic features, such as chronic cough and sputum production, persistent chest radiograph abnormalities, or airway obstruction manifested by wheezing and air trapping; or a history of CF in a sibling; or a positive newborn screening test result; 2. Two CFTR mutations identified of which one is R334W OR only the R334W mutation identified and a sweat chloride value above 60 mmol/L 3. Age 12 years and older 4. Subject will sign and date an informed consent form (ICF) and or assent (for subjects 12 to 16 years old). --- R334W ---

One or more characteristic phenotypic features, such as chronic cough and sputum production, persistent chest radiograph abnormalities, or airway obstruction manifested by wheezing and air trapping; or a history of CF in a sibling; or a positive newborn screening test result; 2. Two CFTR mutations identified of which one is R334W OR only the R334W mutation identified and a sweat chloride value above 60 mmol/L 3. Age 12 years and older 4. Subject will sign and date an informed consent form (ICF) and or assent (for subjects 12 to 16 years old). --- R334W --- --- R334W ---

The R334W-CFTR mutation is a rare mutation (270 subjects in the European CF Registry ECFSPR), described in CFTR2 as disease causing. --- R334W ---

Clinically there is evidence for residual CFTR function in these subjects since only 36% of the patients with R334W are pancreatic insufficient and the mean age of all patients in the CFTR2 database is a bit older (22 years) than patients with CF and 2 known disease causing mutations (20 years). --- R334W ---

On the other hand, patients with R334W have on average a high sweat chloride (mean 95 mmol/L) and severe lung disease; their mean FEV1 reported to the CFTR database [1] is very similar to that of other patients with the F508del CF causing mutation. --- R334W ---

In the Leuven clinic we have one subject with R334W/F508del who is 60 year old and has very severe lung disease (FEV1 in the low 40s). --- R334W ---

When studied in FRT (Fisher rat thyroid) cells and compared to wild type, the R334W mutation is reported to give rise to normal levels of protein at the cell membrane, but very much decreased function (short circuit current measurement) of 1.3% of wild type. --- R334W ---

When tested in intestinal organoids from the patient with F508del/R334W in the Leuven clinic, this mutation resulted in some residual function documented by forskolin induced swelling at higher forskolin concentrations, even before addition of CFTR potentiator or corrector. --- R334W ---

Comparable results are obtained in prof M Amaral's lab in 3 subjects compound heterozygous for F508del/R334W (results in nasal cells, and intestinal organoids). --- R334W ---

A CFTR functional rescue in organoids from a subject with the R334W/R746X is also reported by the Dutch Utrecht group in organoids; the forskolin induced swelling induced by luma/iva was again between the response seen with iva in organoids from subjects with gating mutations and by luma/iva in organoids derived from F508del homozygous subjects. --- R334W ---

These findings suggest that R334W might be a suitable candidate for TEZ/IVA treatment. --- R334W ---

With the present study, the response of organoids of patients with mutation R334W to available CFTR-modulators will be tested to identify the in vitro response. --- R334W ---

Primary Outcomes

Description: Response to tezacaftor+ivacaftor in the Forskolin Induced Swelling (FIS) assay in rectal organoids

Measure: Response to CFTR-modulator in Intestinal Organoids: Increase in Forskolin induced swelling by addition of tezacaftor+ivacaftor after stimulation with Forskolin (0.8 µmol/L)

Time: At study completion (when rectal biopsy is performed or when organoids are retrieved from the biobank and FIS has been performed), an average of 2 months


HPO Nodes