Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001865864 | SCV002307455 | likely pathogenic | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 573 of the CNGA3 protein (p.Tyr573His). This variant is present in population databases (no rsID available, gnomAD 0.06%). This missense change has been observed in individual(s) with clinical feature of achromatopsia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1064475). 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 CNGA3 protein function. This variant disrupts the p.Tyr573 amino acid residue in CNGA3. Other variant(s) that disrupt this residue have been observed in individuals with CNGA3-related conditions (PMID: 11536077; Invitae), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Mendelics | RCV001729876 | SCV002518729 | pathogenic | Achromatopsia 2 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Molecular Genetics Laboratory, |
RCV001729876 | SCV001571309 | likely pathogenic | Achromatopsia 2 | 2021-04-15 | no assertion criteria provided | research |