Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001381007 | SCV001579256 | pathogenic | Dystonia 12 | 2020-07-25 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with ATP1A3-related conditions (PMID: 24431296, Invitae). ClinVar contains an entry for this variant (Variation ID: 161129). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with cysteine at codon 358 of the ATP1A3 protein (p.Gly358Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. 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 ATP1A3 protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly358 amino acid residue in ATP1A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25656163, 26410222). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |