ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.1009G>C (p.Asp337His)

gnomAD frequency: 0.00002  dbSNP: rs776665275
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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 RCV000552977 SCV000658510 uncertain significance Hyperkalemic periodic paralysis 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 337 of the SCN4A protein (p.Asp337His). This variant is present in population databases (rs776665275, gnomAD 0.02%). 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: 477397). 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 not expected to disrupt SCN4A protein function with a negative predictive value of 80%. 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 RCV002506372 SCV002814929 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 2021-07-29 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004735629 SCV005358172 uncertain significance SCN4A-related disorder 2024-07-22 no assertion criteria provided clinical testing The SCN4A c.1009G>C variant is predicted to result in the amino acid substitution p.Asp337His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.020% of alleles in individuals of European (Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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