Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV001074023 | SCV001239590 | likely pathogenic | Retinal dystrophy | 2018-10-30 | criteria provided, single submitter | clinical testing | |
Institute of Medical Molecular Genetics, |
RCV001352956 | SCV001548027 | likely pathogenic | Achromatopsia 2 | 2021-01-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001362275 | SCV001558284 | uncertain significance | not provided | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 376 of the CNGA3 protein (p.Glu376Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individuals with clinical features of achromatopsia (PMID: 20506298, 33546218; Invitae). ClinVar contains an entry for this variant (Variation ID: 866210). 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 CNGA3 protein function. Experimental studies have shown that this missense change affects CNGA3 function (PMID: 20506298). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |