ClinVar Miner

Submissions for variant NM_152296.5(ATP1A3):c.2318A>G (p.Asn773Ser)

dbSNP: rs606231437
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
Institute of Human Genetics, University of Leipzig Medical Center RCV000148319 SCV001440416 pathogenic Alternating hemiplegia of childhood 2 2019-01-01 criteria provided, single submitter clinical testing
3billion, Medical Genetics RCV000148319 SCV002012103 pathogenic Alternating hemiplegia of childhood 2 2021-10-02 criteria provided, single submitter clinical testing Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000161138.2, PS1_S). The missense variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PM1). It is not observed in the gnomAD v2.1.1 dataset (PM2). A different missense change at the same codon (p.Asn773Ile) has been reported as pathogenic (VCV000161139.1, PM5). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.679, PP3). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV002510791 SCV002820658 pathogenic not provided 2024-05-20 criteria provided, single submitter clinical testing 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: 32454213, 35177115, 26417536, 27312461, 24739246, 25447930, 26410222, 27577505, 22842232, 31061839, 31942761)
Labcorp Genetics (formerly Invitae), Labcorp RCV002514853 SCV003443339 pathogenic Dystonia 12 2024-11-11 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 773 of the ATP1A3 protein (p.Asn773Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ATP1A3-related conditions (PMID: 22842232, 32454213). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 161138). 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 ATP1A3 protein function with a positive predictive value of 95%. 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.