ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4222C>T (p.Arg1408Cys)

dbSNP: rs118047588
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688248 SCV000815852 uncertain significance Hyperkalemic periodic paralysis 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1408 of the SCN4A protein (p.Arg1408Cys). This variant is present in population databases (rs118047588, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. ClinVar contains an entry for this variant (Variation ID: 568015). 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%. 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.
Fulgent Genetics, Fulgent Genetics RCV000764140 SCV000895125 uncertain significance Hypokalemic periodic paralysis, type 1; Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16 2018-10-31 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001508990 SCV001715457 uncertain significance not provided 2020-12-29 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001508990 SCV003821279 uncertain significance not provided 2019-12-06 criteria provided, single submitter clinical testing
GeneDx RCV001508990 SCV003852930 uncertain significance not provided 2023-03-29 criteria provided, single submitter clinical testing Reported in one affected individual from a case-control study of atrioventricular nodal re-entry tachycardia; however, specific phenotype information was not provided (Luo et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32508047)

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