ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.1604G>A (p.Arg535Gln) (rs199473121)

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Total submissions: 3
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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 RCV000058435 SCV000089955 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.
Equipe Genetique des Anomalies du Developpement,Université de Bourgogne RCV000677695 SCV000803843 pathogenic Long QT syndrome 3 2016-08-03 criteria provided, single submitter clinical testing
Invitae RCV000638649 SCV000760187 uncertain significance Brugada syndrome 2017-11-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 535 of the SCN5A protein (p.Arg535Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs199473121, ExAC 0.002%). This variant has been reported in several individuals either affected with long QT syndrome or with a suspicion of this condition (PMID: 24349418, 19716085). ClinVar contains an entry for this variant (Variation ID: 67672). Experimental studies have shown that this missense change results in a sodium channel with an increased inactivation time leading to a persistent sodium current and a tendency to prolonged action potential duration (PMID: 24349418). 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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