Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000672144 | SCV000797215 | uncertain significance | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2018-01-16 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000672144 | SCV002236353 | pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2023-08-30 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 556178). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 328 of the RPE65 protein (p.Leu328Phe). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with autosomal recessive early onset retinal dystrophy (PMID: 28393863, 31630094, 35129589). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 not expected to disrupt RPE65 protein function. For these reasons, this variant has been classified as Pathogenic. |