ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4378C>T (p.Arg1460Trp) (rs368256039)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000543330 SCV000658581 uncertain significance Hyperkalemic Periodic Paralysis Type 1 2016-11-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1460 of the SCN4A protein (p.Arg1460Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs368256039, ExAC 0.006%) but has not been reported in the literature in individuals with a SCN4A-related disease. A different missense substitution at this codon (p.Arg1460Gln) has been identified in a family affected with myotonia (PMID: 21752396). 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. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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