Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV001074652 | SCV001240244 | pathogenic | Retinal dystrophy | 2019-02-21 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV001683732 | SCV001905567 | pathogenic | not provided | 2021-09-15 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001683732 | SCV002165328 | pathogenic | not provided | 2024-05-04 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 341 of the CNGA3 protein (p.Ser341Pro). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with achromatopsia (PMID: 11536077, 15712225, 20506298). 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: 866559). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CNGA3 function (PMID: 17693388, 20506298). For these reasons, this variant has been classified as Pathogenic. |