Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001546327 | SCV001765823 | pathogenic | not provided | 2023-06-26 | criteria provided, single submitter | clinical testing | Reported in a patient with progressive dystonia and cognitive disability, as well as a patient with a metabolic or endocrine-related condition not otherwise specified in published literature (Meijer et al., 2016; Klee et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30891744, 24842602, 33144682, 34426522) |
| Labcorp Genetics |
RCV002568966 | SCV003443918 | pathogenic | Dystonia 12 | 2022-07-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 1187017). 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. For these reasons, this variant has been classified as Pathogenic. This missense change has been observed in individual(s) with alternating hemiplegia of childhood (PMID: 24842602). In at least one individual the variant was observed to be de novo. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 893 of the ATP1A3 protein (p.Gly893Arg). This variant is not present in population databases (gnomAD no frequency). |