Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002634317 | SCV003523467 | pathogenic | Familial hemiplegic migraine | 2022-06-08 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ATP1A2 function (PMID: 23838748). 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. This missense change has been observed in individual(s) with autosomal dominant familial hemiplegic migraine (PMID: 23838748). It has also been observed to segregate with disease in related individuals. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1007 of the ATP1A2 protein (p.Arg1007Trp). |
Gene |
RCV003314752 | SCV004014120 | uncertain significance | not provided | 2023-01-12 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate conflicting evidence of the effect of this variant (Pisano et al., 2013); This variant is associated with the following publications: (PMID: 33839563, 30842972, 27818813, 23838748, 28479855, 30258939, 26081103, 27445835) |