ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.664C>T (p.Arg222Trp) (rs527236148)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763022 SCV000893473 likely pathogenic Hypokalemic periodic paralysis 1; Potassium aggravated myotonia; Paramyotonia congenita of von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic Periodic Paralysis Type 1; Congenital myasthenic syndrome, acetazolamide-responsive 2018-10-31 criteria provided, single submitter clinical testing
GeneReviews RCV000132735 SCV000187696 pathogenic Hypokalemic periodic paralysis, type 2 2014-07-31 no assertion criteria provided literature only
Invitae RCV000654671 SCV000776570 pathogenic Hyperkalemic Periodic Paralysis Type 1 2018-08-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 222 of the SCN4A protein (p.Arg222Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported to in segregate with hypokalemic periodic paralysis in several families (PMID: 21189962, 29419865) and has been reported in additional unrelated individuals affected with hypokalemic periodic paralysis (PMID: 19118277, 21841462). ClinVar contains an entry for this variant (Variation ID: 143199). 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. For these reasons, this variant has been classified as Pathogenic.

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