Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001884991 | SCV002162933 | uncertain significance | Cone-rod dystrophy 6; Leber congenital amaurosis 1 | 2022-05-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 761 of the GUCY2D protein (p.Arg761Gln). This variant is present in population databases (rs764439180, gnomAD 0.008%). This missense change has been observed in individuals with clinical features of autosomal dominant cone-rod dystrophy (PMID: 23563732; Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant disrupts the p.Arg761 amino acid residue in GUCY2D. Other variant(s) that disrupt this residue have been observed in individuals with GUCY2D-related conditions (PMID: 32821499), which suggests that this may be a clinically significant amino acid residue. 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. |