ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.1342A>G (p.Met448Val)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003822592 SCV004619265 uncertain significance Hyperkalemic periodic paralysis 2023-01-28 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of SCN4A-related conditions (PMID: 33879512). 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 448 of the SCN4A protein (p.Met448Val).
GeneDx RCV005250331 SCV005901023 uncertain significance not provided 2024-09-23 criteria provided, single submitter clinical testing Reported as heterozygous in an individual with congenital myopathy and scoliosis in the published literature (PMID: 33879512); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33879512)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.