ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.994G>A (p.Ala332Thr) (rs749769938)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000638701 SCV000760243 uncertain significance Brugada syndrome 2017-08-28 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 332 of the SCN5A protein (p.Ala332Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs749769938, ExAC 0.001%). This variant has not been reported in the literature in individuals with a SCN5A-related disease. 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 C55"). This variant identified in the SCN5A gene is located in the transmembrane spanning DI-S5/S6 region of the resulting protein (PMID: 25348405, 12650879), but it is unclear how this variant impacts the function of this protein. 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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