ClinVar Miner

Submissions for variant NM_000219.6(KCNE1):c.163G>A (p.Gly55Ser)

gnomAD frequency: 0.00003  dbSNP: rs199473644
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000150858 SCV000198416 uncertain significance not specified 2014-02-10 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Gly55Ser varian t in KCNE1 has not been previously reported in any individuals with hearing loss and was absent from large population studies. However, this variant has been re ported in one individual with long QT syndrome (Kapplinger 2009). The glycine (G ly) residue at position 55 is not conserved across several species including two mammals (hamster and mole) having serine (Ser) at this position, suggesting tha t the variant may be tolerated. However, this information is not sufficient to r ule out pathogenicity. In summary, the clinical significance of this variant can not be determined with certainty; however based upon the conservation data, we w ould lean towards a more likely benign role.
Invitae RCV000463748 SCV000549147 uncertain significance Long QT syndrome 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 55 of the KCNE1 protein (p.Gly55Ser). This variant is present in population databases (rs199473644, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of LQTS (PMID: 19716085, 31941373). ClinVar contains an entry for this variant (Variation ID: 132657). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects KCNE1 function (PMID: 17545244). 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 RCV000786139 SCV001769652 uncertain significance not provided 2020-12-01 criteria provided, single submitter clinical testing Reported in one individual referred for LQTS genetic testing (Kapplinger et al., 2009); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Reported as a variant of uncertain significance by other clinical laboratories in ClinVar (SCV000549147.3, SCV000198416.4; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 24710009, 19716085, 31941373, 28988457)
Ambry Genetics RCV002399485 SCV002704558 likely benign Cardiovascular phenotype 2022-09-14 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002477299 SCV002785867 uncertain significance Jervell and Lange-Nielsen syndrome 2; Long QT syndrome 5 2021-09-08 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000119069 SCV000153788 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:19716085). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786139 SCV000924805 uncertain significance not provided 2018-01-12 no assertion criteria provided provider interpretation Variant KCNE1 p.Gly55Ser (c.163G>A) exon 4 (NM_000219.5, hg19 chr21-35821770-C-T) SCICD classification variant of uncertain significance, probably benign We do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The rationale for this assessment is: too high MAF. (rs199473644, ExAC 0.07%)" 0.05198% MAF in South Asians

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