Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001963988 | SCV002248142 | pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 530 of the RPE65 protein (p.Phe530Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Leber congenital amaurosis and/or retinitis pigmentosa (PMID: 25383945, 26047050, 33952291). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1470027). 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 with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV003471217 | SCV004209267 | pathogenic | Leber congenital amaurosis 2 | 2024-03-15 | criteria provided, single submitter | clinical testing |