Description
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 801 of the ATP1A3 protein (p.Asp801Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with alternating hemiplegia of childhood (PMID: 22842232, 22850527, 23409136, 24431296, 24842602). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 37107). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ATP1A3 function (PMID: 22842232, 24631656, 25523819, 25681536). This variant disrupts the p.D801 amino acid residue in ATP1A3. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24100174, 26410222). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
