ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.1643G>A (p.Arg548His) (rs121918616)

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
GeneDx RCV000423537 SCV000520966 pathogenic not provided 2018-12-04 criteria provided, single submitter clinical testing The R548H variant was previously reported to segregate with basilar migraine in several relatives from a single family, and it was also identified in one family member with migraine without aura but not in other relatives with isolated migraine (Ambrosini et al., 2005). In vitro functional studies demonstrated that R548H variant results in reduced ATPase activity, alters the affinity for sodium and potassium, and reduces catalytic turnover compared to the wild type protein (Swarts et al., 2013). The R548H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution that occurs at a conserved position predicted to be located in the cytoplasmic phosphorylation subdomain between the M4 and M5 transmembrane domains, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, a different amino acid substitution at the same position (R548C) was identified in a proband with migraine and seizures as well as several relatives with hemiplegic migraine, supporting the functional importance of this residue in the protein (Lebas et al., 2008). Therefore, we interpret the R548H as a pathogenic variant.
OMIM RCV000013789 SCV000034036 pathogenic Migraine, familial basilar 2005-12-13 no assertion criteria provided literature only

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.