Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV000626998 | SCV000747701 | likely pathogenic | Seizure; Apnea; Delayed speech and language development; Hemiplegia; Oculogyric crisis | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002529802 | SCV003461802 | pathogenic | Dystonia 12 | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 320 of the ATP1A3 protein (p.Ala320Pro). 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: 30392204). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 523558). 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 ATP1A3 protein function with a positive predictive value of 95%. This variant disrupts the p.Ala320 amino acid residue in ATP1A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26993267, 31031587). 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. |