Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001932793 | SCV002167790 | pathogenic | not provided | 2023-07-21 | criteria provided, single submitter | clinical testing | 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 ACO2 protein function. ClinVar contains an entry for this variant (Variation ID: 1400671). This missense change has been observed in individuals with optic atrophy (PMID: 34056600). This variant is present in population databases (rs755024692, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 671 of the ACO2 protein (p.Arg671Gln). This variant disrupts the p.Arg671 amino acid residue in ACO2. Other variant(s) that disrupt this residue have been observed in individuals with ACO2-related conditions (PMID: 34056600), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV002292676 | SCV002584975 | pathogenic | Optic atrophy 9 | 2022-10-19 | no assertion criteria provided | literature only |