Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002031094 | SCV002313918 | pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2022-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 135 of the RPE65 protein (p.Asn135Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with RPE65-related conditions (PMID: 30268864, 31736247; Invitae). ClinVar contains an entry for this variant (Variation ID: 1521093). 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 RPE65 protein function. For these reasons, this variant has been classified as Pathogenic. |