ClinVar Miner

Submissions for variant NM_000219.6(KCNE1):c.242A>G (p.Tyr81Cys)

gnomAD frequency: 0.00001  dbSNP: rs199473359
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795910 SCV000935391 uncertain significance Long QT syndrome 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 81 of the KCNE1 protein (p.Tyr81Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with long QT syndrome (PMID: 16155735). ClinVar contains an entry for this variant (Variation ID: 132671). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects KCNE1 function (PMID: 16945797). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001753500 SCV001985330 uncertain significance not provided 2019-08-23 criteria provided, single submitter clinical testing Published functional studies suggest a dominant negative effect (Wu et al., 2006); Reported in ClinVar as a variant of uncertain significance but additional evidence is not available (ClinVar Variant ID# 132671; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 16945797, 22581653, 16945798, 24710009, 17341399, 16155735, 30530868)
Ambry Genetics RCV003162553 SCV003910007 uncertain significance Cardiovascular phenotype 2019-08-13 criteria provided, single submitter clinical testing The c.242A>G (p.Y81C) alteration is located in exon 3 (coding exon 1) of the KCNE1 gene. This alteration results from a A to G substitution at nucleotide position 242, causing the tyrosine (Y) at amino acid position 81 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000119083 SCV000153802 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:16155735;PMID:16945797). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Roden Lab, Vanderbilt University Medical Center RCV004777591 SCV005393508 not provided Long QT syndrome 5 no assertion provided in vitro

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