Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672055 | SCV000797114 | uncertain significance | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2018-01-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001549804 | SCV001770022 | likely pathogenic | not provided | 2021-11-01 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28130426) |
| Invitae | RCV000672055 | SCV002235460 | pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2023-01-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 556104). This missense change has been observed in individual(s) with rod-cone dystrophy (PMID: 28130426). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 252 of the RPE65 protein (p.Phe252Ser). |