ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.4280G>A (p.Arg1427Lys)

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 RCV003790345 SCV004580103 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-04-07 criteria provided, single submitter clinical testing 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1S protein function. This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 1427 of the CACNA1S protein (p.Arg1427Lys).
All of Us Research Program, National Institutes of Health RCV004006014 SCV004815958 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-02-24 criteria provided, single submitter clinical testing This missense variant replaces arginine with lysine at codon 1427 of the CACNA1S protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CACNA1S-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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.