Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000423022 | SCV000535725 | uncertain significance | not provided | 2017-01-05 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ATP1A2 gene. The R514W variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R514W variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R514W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV001070240 | SCV001235458 | uncertain significance | Familial hemiplegic migraine | 2023-08-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 514 of the ATP1A2 protein (p.Arg514Trp). This variant is present in population databases (rs781474239, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 392452). 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 ATP1A2 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. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000423022 | SCV003799073 | uncertain significance | not provided | 2022-12-20 | criteria provided, single submitter | clinical testing | PP3 |