ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.841G>A (p.Val281Met)

gnomAD frequency: 0.00009  dbSNP: rs370289618
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001362781 SCV001558817 uncertain significance Hyperkalemic periodic paralysis 2024-09-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 281 of the SCN4A protein (p.Val281Met). This variant is present in population databases (rs370289618, 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: 1054299). 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.
Ambry Genetics RCV002547802 SCV003654129 uncertain significance Inborn genetic diseases 2022-06-27 criteria provided, single submitter clinical testing The c.841G>A (p.V281M) 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 841, causing the valine (V) at amino acid position 281 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003136028 SCV003818686 uncertain significance not provided 2021-03-20 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005014489 SCV005650918 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 2024-03-11 criteria provided, single submitter clinical testing

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