ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.139C>T (p.Arg47Cys) (rs199472696)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000046072 SCV000074085 pathogenic Long QT syndrome 2020-06-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 174 of the KCNQ1 protein (p.Arg174Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs199472696, ExAC <0.01%). This variant has been reported in the literature in multiple unrelated individuals affected with long QT syndrome (PMID: 9386136, 23392653, 23130128, 15840476, 11668638, 19716085). ClinVar contains an entry for this variant (Variation ID: 53058). Experimental studies have shown that this missense change significantly decreases KCNQ1 protein function (PMID: 9312006, 19934648). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000182078 SCV000234381 pathogenic not provided 2021-02-04 criteria provided, single submitter clinical testing Reported as pathogenic in ClinVar by other clinical laboratories (ClinVar Variant ID# 53058; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Published in vitro functional studies demonstrate a damaging effect as the R174C variant impairs potassium channel regulation and function (Chouabe et al., 1997; Matavel et al., 2010; Wu et al., 2018); This variant is associated with the following publications: (PMID: 32383558, 31737537, 29037160, 26907222, 27761162, 23130128, 10973849, 15840476, 9386136, 26986070, 19815527, 26669661, 23728945, 27251404, 23392653, 19934648, 19716085, 9312006, 22581653, 11668638, 19841300, 29532034, 29449639, 29033053)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587627 SCV000695990 pathogenic Long QT syndrome 1 2016-02-01 criteria provided, single submitter clinical testing Variant summary: The c.520C>T (p.R174C) in KCNQ1 gene is a missense variant that involves a conserved nucleotide and 5/5 in silico tools predict deleterious outcome. The variant is present in the control population dataset of ExAC at a low frequency (0.0008%) which does not exceed the maximum allele frequency for a pathogenic KCNQ1 variant (0.01%). This variant has been reported in the literature in multiple affected individuals presented with elongated QTc interval, including one homozygous pt with severe arrhythmic presentation. Other alterations of the same codon, p.R174H, p.R174L and p.R174P have been reported in pts with LQTS. Functional studies showed p.R174C alters the normal channel activity. In addition, several reputable databases/clinical laboratories classified the variant as Pathogenic. Therefore, this variant was classified as Pathogenic.
Color Health, Inc RCV001184215 SCV001350155 likely pathogenic Arrhythmia 2018-11-04 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057689 SCV000089208 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:9386136;PMID:11668638;PMID:15840476;PMID:19716085;PMID:19934648). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000046072 SCV000804994 pathogenic Long QT syndrome 2015-09-10 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.