ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.1384G>A (p.Glu462Lys) (rs199473572)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000539748 SCV000637081 uncertain significance Brugada syndrome 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 462 of the SCN5A protein (p.Glu462Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs199473572, ExAC 0.01%). This variant has been reported in individuals, affected or with a suspicion of Long QT synrome or affected with Brugada syndrome (PMID: 15840476, 19841300, 24721456). ClinVar contains an entry for this variant (Variation ID: 67660). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant identified in the SCN5A gene is located in the interdomain linker DI/DII region of the resulting protein (PMID: 25348405, 12650879), but it is unclear how this variant impacts the function of this protein. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV001188889 SCV001356061 uncertain significance Arrhythmia 2019-10-09 criteria provided, single submitter clinical testing
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058419 SCV000089939 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:15840476;PMID:19841300;PMID:22378279). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
CSER _CC_NCGL, University of Washington RCV000148862 SCV000190606 uncertain significance Long QT syndrome 2014-06-01 no assertion criteria provided research

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