ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.365G>A (p.Arg122His)

gnomAD frequency: 0.00006  dbSNP: rs374529559
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV002473035 SCV000615088 uncertain significance not provided 2022-01-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000821348 SCV000962102 uncertain significance Hyperkalemic periodic paralysis 2024-12-05 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 122 of the SCN4A protein (p.Arg122His). This variant is present in population databases (rs374529559, gnomAD 0.01%). 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: 448276). 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.
Revvity Omics, Revvity RCV002473035 SCV003818677 uncertain significance not provided 2022-05-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV004669018 SCV005157676 uncertain significance Inborn genetic diseases 2024-04-23 criteria provided, single submitter clinical testing The c.365G>A (p.R122H) alteration is located in exon 2 (coding exon 2) of the SCN4A gene. This alteration results from a G to A substitution at nucleotide position 365, causing the arginine (R) at amino acid position 122 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005018886 SCV005650933 uncertain significance Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16; Congenital myopathy 22A, classic; Congenital myopathy 22B, severe fetal 2023-12-29 criteria provided, single submitter clinical testing

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