ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.2150T>C (p.Val717Ala)

dbSNP: rs1567823095
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000713095 SCV000843664 uncertain significance not provided 2020-12-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001346721 SCV001540945 likely pathogenic Familial hyperkalemic periodic paralysis 2023-11-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 717 of the SCN4A protein (p.Val717Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant SCN4A-related conditions (PMID: 23771340; Invitae). ClinVar contains an entry for this variant (Variation ID: 586508). 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 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.
GeneDx RCV000713095 SCV001874735 uncertain significance not provided 2023-12-04 criteria provided, single submitter clinical testing Previously identified in an individual with a clinical diagnosis of myotonia, however, further clinical details were not provided (PMID: 23771340); 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: 23771340)

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.