Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003031219 | SCV003322388 | uncertain significance | Cone-rod dystrophy 13; Leber congenital amaurosis 6 | 2022-02-27 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs565837539, gnomAD 0.005%), including at least one homozygous and/or hemizygous individual. 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. This variant disrupts the p.Glu800 amino acid residue in RPGRIP1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24123792, 26047050; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with RPGRIP1-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 800 of the RPGRIP1 protein (p.Glu800Gln). |