ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.2014C>G (p.Arg672Gly)

dbSNP: rs80338785
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206901 SCV001232729 pathogenic Familial hyperkalemic periodic paralysis 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 672 of the SCN4A protein (p.Arg672Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypokalemic periodic paralysis (PMID: 10944223, 18162704, 19225109). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5913). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SCN4A protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SCN4A function (PMID: 10944223, 11912116, 17330043, 18824591, 20660662). This variant disrupts the p.Arg672 amino acid residue in SCN4A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10944223, 11558801, 15482957, 18824591, 23019082). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001092728 SCV001249368 pathogenic not provided 2019-04-01 criteria provided, single submitter clinical testing
OMIM RCV000006276 SCV000026458 pathogenic Hypokalemic periodic paralysis, type 2 2002-04-01 no assertion criteria provided literature only
GeneReviews RCV000006276 SCV000040616 not provided Hypokalemic periodic paralysis, type 2 no assertion provided literature only
GeneReviews RCV000206901 SCV000262564 not provided Familial hyperkalemic periodic paralysis no assertion provided literature only
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences RCV000020262 SCV002600055 pathogenic Hypokalemic periodic paralysis, type 1 2022-04-12 no assertion criteria provided research

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