Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002011018 | SCV002296384 | uncertain significance | Familial hemiplegic migraine | 2022-08-09 | criteria provided, single submitter | clinical testing | 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. 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 not expected to disrupt ATP1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 1502529). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. This variant is present in population databases (rs748654627, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 514 of the ATP1A2 protein (p.Arg514Leu). |
| Ambry Genetics | RCV002398087 | SCV002706258 | uncertain significance | Inborn genetic diseases | 2018-03-13 | criteria provided, single submitter | clinical testing | The p.R514L variant (also known as c.1541G>T), located in coding exon 12 of the ATP1A2 gene, results from a G to T substitution at nucleotide position 1541. The arginine at codon 514 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |