ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.4349T>A (p.Val1450Asp) (rs199473252)

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Total submissions: 2
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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 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.
Invitae RCV000058665 SCV000637154 uncertain significance Brugada syndrome 2017-08-21 criteria provided, single submitter clinical testing This sequence change replaces valine with aspartic acid at codon 1451 of the SCN5A protein (p.Val1451Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. This variant is not present in population databases (rs199473252, ExAC no frequency). This variant has been reported in an individual referred for Brugada syndrome genetic testing (PMID: 20129283). ClinVar contains an entry for this variant (Variation ID: 67885). 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: "Benign"; Align-GVGD: "Class C65"). This variant identified in the SCN5A gene is located in the transmembrane DIII-S6 region of the resulting protein (PMID: 25348405). For more information about the location of this variant, please visit www.invitae.com/SCN5A-topology. 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. While it is absent from the population and reported in a possibly affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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