ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1697C>T (p.Ser566Leu) (rs199473435)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000203863 SCV000260666 uncertain significance Long QT syndrome 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 906 of the KCNH2 protein (p.Ser906Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. While this variant is not present in population databases (rs199473435), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in several individuals referred for long QT syndrome testing (PMID: 19716085, 26743238). ClinVar contains an entry for this variant (Variation ID: 67429). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000455329 SCV000539442 uncertain significance not specified 2016-06-23 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 2 probands.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000203863 SCV000748010 uncertain significance Long QT syndrome 2017-02-06 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765943 SCV000897364 uncertain significance Short QT syndrome 1; Long QT syndrome 2 2018-10-31 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058154 SCV000089674 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.

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