ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.6031C>T (p.Arg2011Cys) (rs199473640)

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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 RCV000058827 SCV000090347 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.
Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues RCV000515713 SCV000611766 uncertain significance Long QT syndrome 3 2017-07-07 criteria provided, single submitter clinical testing
Color RCV000771791 SCV000904480 uncertain significance Arrhythmia 2018-05-29 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This variant is a missense variant located in the C-terminal region of the SCN5A protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual referred for long QT testing (PMID: 19716085), as well as in a control subject (PMID: 19406494). This variant has been identified in 8/184766 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000468309 SCV000545060 uncertain significance Brugada syndrome 2016-08-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 2012 of the SCN5A protein (p.Arg2012Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs199473640, ExAC 0.02%) and was reported in one control individual (PMID: 19406494). This variant was reported in individuals referred for long QT testing (PMID: 19716085) ClinVar contains an entry for this variant (Variation ID: 68027). This variant identified in the SCN5A gene is located in the cytoplasmic C-terminal region of the resulting protein (PMID: 25348405), but it is unclear how this variant impacts the function of this protein. 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"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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