ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.536G>A (p.Arg179Gln)

gnomAD frequency: 0.00001  dbSNP: rs777130479
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002036995 SCV002318222 uncertain significance Hyperkalemic periodic paralysis 2024-11-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 179 of the SCN4A protein (p.Arg179Gln). This variant is present in population databases (rs777130479, gnomAD 0.007%). 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: 1525847). 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 expected to disrupt SCN4A protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect SCN4A function (PMID: 29605429). 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 RCV002479840 SCV002779577 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 2022-04-21 criteria provided, single submitter clinical testing
GeneDx RCV003328693 SCV004035881 uncertain significance not provided 2023-03-17 criteria provided, single submitter clinical testing Observed in unaffected individuals in published literature (Mnnikk et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); 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: 29605429)

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