ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.880G>A (p.Val294Met) (rs199473086)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000455194 SCV000540292 uncertain significance not specified 2016-10-20 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 1 BrS proband (PMID 11901046) and as secondary finding in a WES case.
Invitae RCV000058857 SCV000760271 uncertain significance Brugada syndrome 2020-09-20 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 294 of the SCN5A protein (p.Val294Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs199473086, ExAC 0.006%). This variant has been reported in an individual affected with Brugada syndrome (PMID: 11901046). ClinVar contains an entry for this variant (Variation ID: 68054). Experimental studies have shown that this missense change disrupts channel function (PMID: 21840964). 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.
Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues RCV000678952 SCV000805167 uncertain significance Long QT syndrome 3 2018-04-25 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765741 SCV000897109 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1, autosomal recessive; Progressive familial heart block, type 1A; Paroxysmal familial ventricular fibrillation 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2018-10-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV000777706 SCV000913649 uncertain significance Arrhythmia 2019-05-14 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000998027 SCV001153885 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000998027 SCV001804355 uncertain significance not provided 2021-04-01 criteria provided, single submitter clinical testing Reported in association with arrhythmia (Priori et al., 2000; Marschall et al., 2019); however, detailed clinical information was not provided; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 68054; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies demonstrate a small but significant reduction of sodium current density in V294M SCN5A channels, though, it is not known whether this finding is physiologically relevant in vivo (Shinlapawittayatorn et al., 2011); This variant is associated with the following publications: (PMID: 33221895, 11901046, 14961552, 11076825, 21840964, 14753626, 27711072, 30662450, 31737537)
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058857 SCV000090377 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:11901046;PMID:11076825). 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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