ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4916G>A (p.Arg1639His)

gnomAD frequency: 0.00006  dbSNP: rs368186423
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000817315 SCV000957868 uncertain significance Hyperkalemic periodic paralysis 2025-01-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1639 of the SCN4A protein (p.Arg1639His). This variant is present in population databases (rs368186423, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of SCN4A-related conditions (PMID: 32798841, 35866763, 36116128). ClinVar contains an entry for this variant (Variation ID: 660181). 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%. Experimental studies have shown that this missense change does not substantially affect SCN4A function (PMID: 36116128). 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 RCV002487806 SCV002780951 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 2022-03-15 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003141840 SCV003821318 uncertain significance not provided 2022-09-27 criteria provided, single submitter clinical testing
Athena Diagnostics RCV004997377 SCV005622313 likely benign not specified 2024-01-02 criteria provided, single submitter clinical testing

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