ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4343G>T (p.Arg1448Leu)

dbSNP: rs121908545
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000713109 SCV000843680 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000713109 SCV002019135 likely pathogenic not provided 2019-09-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002532949 SCV003442458 likely pathogenic Hyperkalemic periodic paralysis 2022-04-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 1448 of the SCN4A protein (p.Arg1448Leu). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg1448 amino acid residue in SCN4A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1316765, 7809121, 8005599, 16801039). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 586518). This missense change has been observed in individuals with clinical features of paramyotonia congenita (PMID: 18166706; Invitae). This variant is not present in population databases (gnomAD no frequency).

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