ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.91C>T (p.Arg31Trp)

gnomAD frequency: 0.00001  dbSNP: rs756059775
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001763055 SCV001989152 uncertain significance not provided 2019-12-05 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002477931 SCV002794025 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 2022-05-11 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001763055 SCV003821277 uncertain significance not provided 2021-03-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV003365444 SCV004054565 uncertain significance Inborn genetic diseases 2023-08-20 criteria provided, single submitter clinical testing The c.91C>T (p.R31W) alteration is located in exon 1 (coding exon 1) of the SCN4A gene. This alteration results from a C to T substitution at nucleotide position 91, causing the arginine (R) at amino acid position 31 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003505181 SCV004272316 uncertain significance Hyperkalemic periodic paralysis 2024-04-13 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 31 of the SCN4A protein (p.Arg31Trp). This variant is present in population databases (rs756059775, gnomAD 0.05%). 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: 1303597). 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.

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