Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000811387 | SCV000951652 | pathogenic | Familial hemiplegic migraine | 2024-05-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 324 of the ATP1A2 protein (p.Gly324Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with alternating hemiplesia and/or developmental and epileptic encephalopathy (PMID: 33794876; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 655259). 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 not expected to disrupt ATP1A2 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV001538751 | SCV001756443 | likely pathogenic | not provided | 2024-03-06 | 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; This variant is associated with the following publications: (PMID: 33794876, 37142513) |
Revvity Omics, |
RCV001538751 | SCV003832794 | uncertain significance | not provided | 2019-10-19 | flagged submission | clinical testing |