ClinVar Miner

Submissions for variant NM_000702.4(ATP1A2):c.1816G>A (p.Ala606Thr)

dbSNP: rs1414742926
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520358 SCV000617440 pathogenic not provided 2022-11-16 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect on sodium-potassium pump function (Tavraz et al., 2008; Jen et al., 2007); 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: 17435187, 21908445, 18451712, 22940869, 22067897, 18184292, 29486580, 28445178, 16088919, 24498617, 18728015)
Labcorp Genetics (formerly Invitae), Labcorp RCV001385316 SCV001585131 pathogenic Familial hemiplegic migraine 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 606 of the ATP1A2 protein (p.Ala606Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal dominant familial hemiplegic migraine (PMID: 16088919, 24498617). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 449379). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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: 18728015). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003419903 SCV004109633 pathogenic ATP1A2-related disorder 2023-06-28 criteria provided, single submitter clinical testing The ATP1A2 c.1816G>A variant is predicted to result in the amino acid substitution p.Ala606Thr. This variant was reported in the heterozygous state in numerous individuals with hemiplegic migraine and was found to co-segregate in at least four unrelated families (Riant et al. 2005. PubMed ID: 16088919; Jen et al. 2007. PubMed ID: 17435187; Podestà et al. 2011. PubMed ID: 21908445; Carreño et al. 2013. PubMed ID: 24498617; Hiekkala et al. 2018. PubMed ID: 29486580). Functional studies showed that this variant alters the sodium–potassium pump function (Tavraz et al. 2008. PubMed ID: 18728015). This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-160100376-G-A). This variant is interpreted as pathogenic.
Clinical Genetics Laboratory, Skane University Hospital Lund RCV000520358 SCV005199633 pathogenic not provided 2023-07-26 criteria provided, single submitter clinical testing

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.