ClinVar Miner

Submissions for variant NM_000335.4(SCN5A):c.73G>A (p.Glu25Lys) (rs747251132)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171704 SCV000055212 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Invitae RCV000687411 SCV000814975 uncertain significance Brugada syndrome 2018-02-10 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 25 of the SCN5A protein (p.Glu25Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs747251132, ExAC 0.006%). This variant has been reported in an individual affected with atrial fibrillation (PMID: 28837624). ClinVar contains an entry for this variant (Variation ID: 191505). 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. This variant identified in the SCN5A gene is located in the cytoplasmic N-terminal region of the resulting protein (PMID: 25348405), 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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