Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001913948 | SCV002188923 | uncertain significance | Cone-rod dystrophy 13; Leber congenital amaurosis 6 | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 650 of the RPGRIP1 protein (p.Pro650Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs769167245, ExAC 0.006%). This variant has not been reported in the literature in individuals with RPGRIP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |