ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.310C>T (p.Arg104Cys) (rs199473457)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182100 SCV000234403 pathogenic not provided 2021-05-11 criteria provided, single submitter clinical testing Reported in ClinVar as a pathogenic/likely pathogenic variant (ClinVar Variant ID #53086; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published in vitro functional studies demonstrate this variant alters cell surface expression and potassium current kinetics (Bartos et al., 2011; Henrion et al., 2012; Huang et al., 2021); This variant is associated with the following publications: (PMID: 15176425, 16922724, 28479515, 22509038, 23158531, 33322401, 23193492, 19843919, 22613981, 14998624, 12205790, 19716085, 27761162, 17947213, 27291509, 27807201, 28185290, 28341588, 32048431, 31737537, 32383558, 33600800, 20850564)
Center for Medical Genetics Ghent,University of Ghent RCV000240642 SCV000299261 likely pathogenic Long QT syndrome 1 2016-03-17 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000240642 SCV000583963 pathogenic Long QT syndrome 1 2017-01-12 criteria provided, single submitter research
Invitae RCV001385527 SCV001585409 pathogenic Long QT syndrome 2020-10-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 231 of the KCNQ1 protein (p.Arg231Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with long QT syndrome and/or atrial fibrillation, and segregates with KCNQ1-related conditions in several families (PMID: 22613981, 12205790, 20850564). ClinVar contains an entry for this variant (Variation ID: 53086). Experimental studies have shown that this missense change alters potassium channel function (PMID: 19843919, 22613981, 20850564, 22509038). This variant disrupts the p.Arg231 amino acid residue in KCNQ1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 16414944, 23350853, 24861447), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057733 SCV000089252 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:12205790;PMID:14998624;PMID:15176425;PMID:16922724;PMID:19716085;PMID:19843919;PMID:20850564;PMID:22613981). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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