Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV000850517 | SCV000992721 | likely pathogenic | Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome; Dystonia 12; Alternating hemiplegia of childhood 2 | 2018-10-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001039394 | SCV001202924 | pathogenic | Dystonia 12 | 2023-05-01 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 689735). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly947 amino acid residue in ATP1A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22842232, 24100174, 24523486, 24842602, 24996492, 25996915, 26410222, 26993267). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This missense change has been observed in individual(s) with clinical features of an ATP1A3-related condition (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 947 of the ATP1A3 protein (p.Gly947Trp). |