ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.1139G>A (p.Arg380Gln)

gnomAD frequency: 0.00007  dbSNP: rs374446143
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000691899 SCV000819698 uncertain significance Hyperkalemic periodic paralysis 2023-12-31 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 380 of the SCN4A protein (p.Arg380Gln). This variant is present in population databases (rs374446143, gnomAD 0.009%). 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: 570912). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN4A protein function. 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 RCV000764144 SCV000895129 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 2021-07-07 criteria provided, single submitter clinical testing
Athena Diagnostics RCV001288736 SCV001476051 uncertain significance not provided 2020-07-20 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001288736 SCV001715458 uncertain significance not provided 2021-01-20 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001288736 SCV003821280 uncertain significance not provided 2023-12-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004689856 SCV005184877 uncertain significance not specified 2024-05-10 criteria provided, single submitter clinical testing Variant summary: SCN4A c.1139G>A (p.Arg380Gln) results in a conservative amino acid change located in the ion transport domain (IPR005821) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.5e-05 in 230076 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in SCN4A causing SCN4A-related conditions, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1139G>A in individuals affected with SCN4A-realted conditions and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 570912). Based on the evidence outlined above, the variant was classified as uncertain significance.

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