Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001972146 | SCV002209411 | uncertain significance | Dystonia 12 | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 636 of the ATP1A3 protein (p.Ala636Thr). This variant is present in population databases (rs782744167, gnomAD 0.03%). 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: 1435191). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ATP1A3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
New York Genome Center | RCV002266066 | SCV002548857 | uncertain significance | Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome; Dystonia 12; Alternating hemiplegia of childhood 2 | 2021-08-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002561520 | SCV003709746 | likely benign | Inborn genetic diseases | 2021-07-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |