Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001854256 | SCV002237805 | pathogenic | Retinitis pigmentosa 12; Leber congenital amaurosis 8 | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 638 of the CRB1 protein (p.Ser638Leu). This variant is present in population databases (rs267598278, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of CRB1-related conditions (PMID: 28041643, 33576794, 33633436). 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: 73455). 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 CRB1 protein function with a positive predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
| Dept Of Ophthalmology, |
RCV000505040 | SCV004705153 | likely pathogenic | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research | |
| Baylor Genetics | RCV004566911 | SCV005058545 | likely pathogenic | Leber congenital amaurosis 8 | 2024-03-21 | criteria provided, single submitter | clinical testing | |
| NIHR Bioresource Rare Diseases, |
RCV000505040 | SCV000598911 | likely pathogenic | Retinal dystrophy | 2015-01-01 | no assertion criteria provided | research |