ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.845G>A (p.Arg282His)

gnomAD frequency: 0.00025  dbSNP: rs200615763
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000702949 SCV000831826 uncertain significance Hyperkalemic periodic paralysis 2025-01-29 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 282 of the SCN4A protein (p.Arg282His). This variant is present in population databases (rs200615763, gnomAD 0.07%). 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: 579612). 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) has been performed 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 RCV000765379 SCV000896652 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 2022-03-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002533672 SCV003687618 uncertain significance Inborn genetic diseases 2023-12-06 criteria provided, single submitter clinical testing The c.845G>A (p.R282H) alteration is located in exon 6 (coding exon 6) of the SCN4A gene. This alteration results from a G to A substitution at nucleotide position 845, causing the arginine (R) at amino acid position 282 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003140114 SCV003818762 uncertain significance not provided 2021-07-22 criteria provided, single submitter clinical testing
GeneDx RCV003140114 SCV005078188 uncertain significance not provided 2024-02-27 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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