Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001229312 | SCV001401754 | pathogenic | Familial hemiplegic migraine | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 378 of the ATP1A2 protein (p.Thr378Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with alternating hemiplegia (PMID: 15174025, 15286158). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12921). 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 ATP1A2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ATP1A2 function (PMID: 15286158, 34384358). This variant disrupts the p.Thr378 amino acid residue in ATP1A2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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. |
| Institute of Human Genetics, |
RCV000013784 | SCV001428708 | likely pathogenic | Alternating hemiplegia of childhood 1 | 2019-09-16 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000013784 | SCV000034031 | pathogenic | Alternating hemiplegia of childhood 1 | 2004-08-01 | no assertion criteria provided | literature only |