ClinVar Miner

Submissions for variant NM_152296.5(ATP1A3):c.2887G>A (p.Gly963Ser)

gnomAD frequency: 0.00001  dbSNP: rs200582951
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001319742 SCV001510502 likely pathogenic Dystonia 12 2024-09-10 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 963 of the ATP1A3 protein (p.Gly963Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATP1A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1020197). 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%. This variant disrupts the p.Gly963 amino acid residue in ATP1A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 36114075). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004548160 SCV004109978 uncertain significance ATP1A3-related disorder 2023-02-06 criteria provided, single submitter clinical testing The ATP1A3 c.2926G>A variant is predicted to result in the amino acid substitution p.Gly976Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-42471848-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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