Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000519075 | SCV000621234 | uncertain significance | not provided | 2017-10-09 | criteria provided, single submitter | clinical testing | The G664S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G664S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The G664S 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. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV001858028 | SCV002175227 | uncertain significance | Familial hemiplegic migraine | 2023-05-15 | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ATP1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 452425). This variant has not been reported in the literature in individuals affected with ATP1A2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 664 of the ATP1A2 protein (p.Gly664Ser). |