ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.4349T>A (p.Val1450Asp)

gnomAD frequency: 0.00001  dbSNP: rs199473252
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003764738 SCV000637154 uncertain significance not provided 2024-07-08 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1451 of the SCN5A protein (p.Val1451Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 20129283). ClinVar contains an entry for this variant (Variation ID: 67885). 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 tolerated. 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.
All of Us Research Program, National Institutes of Health RCV003996543 SCV004832047 uncertain significance Cardiac arrhythmia 2024-08-13 criteria provided, single submitter clinical testing This missense variant replaces valine with aspartic acid at codon 1451 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 an individual suspected with Brugada syndrome (PMID: 20129283). This variant has not been identified 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.
GeneDx RCV003764738 SCV005324957 uncertain significance not provided 2024-03-14 criteria provided, single submitter clinical testing Identified in a patient with suspected Brugada syndrome, but additional clinical information was not included and it is unknown whether this individual was screened for variants in other genes associated with Brugada syndrome (PMID: 20129283); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30662450, 30203441, 20129283)
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000058665 SCV000090185 not provided Brugada syndrome no assertion provided literature only This variant has been reported as associated with Brugada syndrome in the following publications (PMID:20129283). 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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