ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.4786G>A (p.Val1596Met)

gnomAD frequency: 0.00003  dbSNP: rs199473279
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003541166 SCV001518065 uncertain significance not provided 2023-07-03 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 67925). This missense change has been observed in individual(s) with Romano-Ward syndrome (PMID: 19862833). This variant is present in population databases (rs199473279, gnomAD 0.007%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1597 of the SCN5A protein (p.Val1597Met).
Fulgent Genetics, Fulgent Genetics RCV002504974 SCV002815971 uncertain significance Brugada syndrome 1; Long QT syndrome 3; Sick sinus syndrome 1; Progressive familial heart block, type 1A; Ventricular fibrillation, paroxysmal familial, type 1; Dilated cardiomyopathy 1E; SUDDEN INFANT DEATH SYNDROME; Atrial fibrillation, familial, 10 2021-07-16 criteria provided, single submitter clinical testing
KardioGenetik, Herz- und Diabeteszentrum NRW RCV003509486 SCV004363572 uncertain significance Long QT syndrome 3 2023-11-08 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003996545 SCV004821685 uncertain significance Cardiac arrhythmia 2023-11-28 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 1597 of the SCN5A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with Romano-Ward syndrome (PMID: 19862833), arrhythmogenic right ventricular cardiomyopathy (PMID: 26383259), or Brugada syndrome (PMID: 34034907), and in an individual with atrioventricular reentrant tachycardia and drug-induced type 1 Brugada pattern (PMID: 29953624). This variant has been identified in 5/279490 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000058708 SCV000090228 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:19862833). 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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