ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.1192G>A (p.Ala398Thr)

gnomAD frequency: 0.00001  dbSNP: rs1174261819
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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 RCV000555432 SCV000658513 uncertain significance Hyperkalemic periodic paralysis 2024-12-08 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 398 of the SCN4A protein (p.Ala398Thr). This variant is not present in population databases (gnomAD no frequency). 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: 477398). 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.
GeneDx RCV001539814 SCV001757627 uncertain significance not provided 2019-10-15 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002497196 SCV002775809 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 2022-05-01 criteria provided, single submitter clinical testing

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