Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000521836 | SCV000617441 | pathogenic | not provided | 2023-01-13 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect (Vanmolkot et al., 2006; Schack et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23561701, 16538223, 23202128, 27445835, 18184292, 18846413, 22117059) |
Ce |
RCV000521836 | SCV001249778 | pathogenic | not provided | 2023-03-01 | criteria provided, single submitter | clinical testing | ATP1A2: PP1:Strong, PM1, PM2, PS4:Moderate, PP3, PS3:Supporting |
Invitae | RCV001385317 | SCV001585132 | pathogenic | Familial hemiplegic migraine | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 628 of the ATP1A2 protein (p.Val628Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with familial hemiplegic migraine (PMID: 16538223). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 449380). 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: 16538223). For these reasons, this variant has been classified as Pathogenic. |