Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002634294 | SCV003523305 | likely pathogenic | Leber congenital amaurosis 2; Retinitis pigmentosa 20 | 2023-07-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 104 of the RPE65 protein (p.Gly104Ser). This variant is present in population databases (rs767478543, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive RPE65-related conditions (PMID: 26667666, 30268864, 33090715). ClinVar contains an entry for this variant (Variation ID: 2202770). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts the p.Gly104 amino acid residue in RPE65. Other variant(s) that disrupt this residue have been observed in individuals with RPE65-related conditions (PMID: 19117922, 25356976, 26355662, 28945494), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Baylor Genetics | RCV003465996 | SCV004209255 | pathogenic | Leber congenital amaurosis 2 | 2023-07-21 | criteria provided, single submitter | clinical testing |