ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.3536C>T (p.Ala1179Val) (rs41310765)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058575 SCV000090095 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:19808398;PMID:22247482).
Color RCV000771383 SCV000903707 likely benign Arrhythmia 2018-04-23 criteria provided, single submitter clinical testing
GeneDx RCV000212992 SCV000235446 likely benign not specified 2017-05-02 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000525661 SCV000637137 uncertain significance Brugada syndrome 2018-08-21 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 1180 of the SCN5A protein (p.Ala1180Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs41310765, ExAC 0.2%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed to segregate with long QT syndrome in a family (PMID: 23963187) and in another family with atrioventricular conduction block and dilated cardiomyopathy (PMID: 19808398). It has also been observed in an individual with progressive familial heart block (PMID: 22247482) and in an individual who died unexpectedly (PMID: 24631775). It has also been observed in a control individual (PMID: 25904541). ClinVar contains an entry for this variant (Variation ID: 67801). Experimental studies have shown that this missense change affects sodium current modulation in the long form of the SCN5A protein (PMID: 19808398). 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.

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