ClinVar Miner

Submissions for variant NM_198056.2(SCN5A):c.2204C>T (p.Ala735Val) (rs137854611)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000058488 SCV000545017 likely pathogenic Brugada syndrome 2016-10-06 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 735 of the SCN5A protein (p.Ala735Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs137854611, ExAC 0.01%). This variant has been reported in individuals affected with sudden unexplained nocturnal death syndrome and Brugada syndrome (PMID: 11823453, 17697823), and was observed in several individuals referred for Brugada syndrome genetic testing (PMID: 20129283). ClinVar contains an entry for this variant (Variation ID: 9391). This variant identified in the SCN5A gene is located in the transmembrane DII-S1 region of the resulting protein (PMID: 25348405). Experimental studies have shown that this variant results in the dysregulation of the voltage channel encoded by the SCN5A gene (PMID: 11823453, 26283144) . In summary this variant is a rare missense change that has been observed in individuals affected with Brugada syndrome and has been shown to affect SCN5A function. For these reasons, this variant has been classified as Likely Pathogenic.
OMIM RCV000009989 SCV000030210 pathogenic Brugada syndrome 1 2002-02-01 no assertion criteria provided literature only
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058488 SCV000090008 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:11823453;PMID:20129283;PMID:22795782). 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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