Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000435735 | SCV000533279 | uncertain significance | not provided | 2016-10-26 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ATP1A2 gene. The Q554L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q554L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV001851068 | SCV002215883 | uncertain significance | Familial hemiplegic migraine | 2022-10-03 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs199749129, gnomAD 0.01%). This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 554 of the ATP1A2 protein (p.Gln554Leu). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. 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: 390448). |