ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.172G>A (p.Glu58Lys)

dbSNP: rs199473413
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000472868 SCV000543435 likely pathogenic Long QT syndrome 2022-07-15 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects KCNH2 function (PMID: 25417810). 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 67254). This missense change has been observed in individuals with long QT syndrome (PMID: 11222472, 19695459; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 58 of the KCNH2 protein (p.Glu58Lys). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV001582554 SCV001818565 likely pathogenic not provided 2024-07-09 criteria provided, single submitter clinical testing Identified in patients with LQTS referred for genetic testing at GeneDx and in the published literature (PMID: 11222472, 19695459, 36861347); Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies suggest a damaging effect via a trafficking defect (PMID: 25417810); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32475984, 11222472, 35688148, 36861347, 22396785, 19695459, 25417810)
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000057966 SCV000089486 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:11222472). 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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