ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.1642C>T (p.Arg548Cys)

dbSNP: rs1651731153
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
CeGaT Center for Human Genetics Tuebingen RCV001092182 SCV001248569 pathogenic not provided 2019-07-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003584837 SCV004292941 pathogenic Familial hemiplegic migraine 2023-10-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 548 of the ATP1A2 protein (p.Arg548Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant ATP1A2-related conditions (PMID: 18498390, 28811059; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 871961). 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 expected to disrupt ATP1A2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ATP1A2 function (PMID: 23954377, 34384358). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Arg548 amino acid residue in ATP1A2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16344534; Invitae; Maksemous et al. 2019 Cephalagia Reports Vol. 2). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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.