Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000186805 | SCV000240374 | uncertain significance | not provided | 2018-10-25 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the ATP1A2 gene. The R92C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R92C variant is observed in 2/30782 (0.01%) alleles from individuals of South Asian background (Lek et al., 2016). The R92C 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in individuals with ATP1A2-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV005089935 | SCV005790945 | uncertain significance | Familial hemiplegic migraine | 2025-01-12 | 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 92 of the ATP1A2 protein (p.Arg92Cys). This variant is present in population databases (rs796052278, gnomAD 0.006%). 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: 204903). 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. |