Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000699311 | SCV000828016 | uncertain significance | Familial hemiplegic migraine | 2025-01-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 348 of the ATP1A2 protein (p.Arg348His). This variant is not present in population databases (gnomAD no frequency). 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: 576743). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ATP1A2 protein function with a negative 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 | RCV002316000 | SCV000847903 | uncertain significance | Inborn genetic diseases | 2018-05-22 | criteria provided, single submitter | clinical testing | The p.R348H variant (also known as c.1043G>A), located in coding exon 9 of the ATP1A2 gene, results from a G to A substitution at nucleotide position 1043. The arginine at codon 348 is replaced by histidine, an amino acid with highly similar properties. A different alteration located at the same position, p.R348P (c.1043G>C), was detected in fourteen individuals from one family. Twelve of these individuals carrying the p.R348P alteration had clinically diagnosed familial hemiplegic migraine (FHM), one had psychomotor retardation and possible FHM, and one did not have FHM features (Pelzer N et al. Cephalalgia, 2016 May). 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 the p.R348H alteration remains unclear. |