ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.5218C>T (p.Arg1740Trp)

gnomAD frequency: 0.00006  dbSNP: rs373804267
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001304994 SCV001494303 uncertain significance Hyperkalemic periodic paralysis 2024-11-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1740 of the SCN4A protein (p.Arg1740Trp). This variant is present in population databases (rs373804267, gnomAD 0.01%). 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: 1007765). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SCN4A protein function with a negative 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.
Genetics and Molecular Pathology, SA Pathology RCV002466658 SCV002761910 uncertain significance Paramyotonia congenita of Von Eulenburg 2021-12-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002486185 SCV002790772 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 2022-02-07 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV001579567 SCV001807719 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001579567 SCV001956961 uncertain significance not provided no assertion criteria provided clinical testing

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