Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000440880 | SCV000533010 | uncertain significance | not provided | 2016-10-24 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ATP1A2 gene. The V924M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V924M variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This substitution occurs at a position that is conserved across species. However, the V924M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV000635217 | SCV000756600 | uncertain significance | Familial hemiplegic migraine | 2023-01-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 390229). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 924 of the ATP1A2 protein (p.Val924Met). This variant is present in population databases (rs373276446, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. 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 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. |
| Fulgent Genetics, |
RCV000763752 | SCV000894638 | uncertain significance | Alternating hemiplegia of childhood 1; Migraine, familial hemiplegic, 2 | 2018-10-31 | criteria provided, single submitter | clinical testing |