Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000693384 | SCV000821251 | uncertain significance | Familial hemiplegic migraine | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 510 of the ATP1A2 protein (p.Arg510Cys). This variant is present in population databases (rs750109401, gnomAD 0.002%). 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: 572079). 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 with a positive predictive value of 80%. 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. |
| Ambry Genetics | RCV002531468 | SCV003555320 | uncertain significance | Inborn genetic diseases | 2022-07-26 | criteria provided, single submitter | clinical testing | The c.1528C>T (p.R510C) alteration is located in exon 12 (coding exon 12) of the ATP1A2 gene. This alteration results from a C to T substitution at nucleotide position 1528, causing the arginine (R) at amino acid position 510 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |