ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.2503T>G (p.Ser835Ala) (rs1421700935)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000638691 SCV000760231 uncertain significance Brugada syndrome 2017-09-19 criteria provided, single submitter clinical testing This sequence change replaces serine with alanine at codon 835 of the SCN5A protein (p.Ser835Ala). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN5A-related disease. This variant identified in the SCN5A gene is located in the transmembrane spanning DII-S4/S5 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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