Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001316864 | SCV001507504 | uncertain significance | Familial hemiplegic migraine | 2022-12-06 | 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: 1017675). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. This variant is present in population databases (rs773318002, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 493 of the ATP1A2 protein (p.Arg493Gln). |
| Ambry Genetics | RCV002395675 | SCV002700366 | uncertain significance | Inborn genetic diseases | 2018-07-06 | criteria provided, single submitter | clinical testing | The p.R493Q variant (also known as c.1478G>A), located in coding exon 12 of the ATP1A2 gene, results from a G to A substitution at nucleotide position 1478. The arginine at codon 493 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |