Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001378739 | SCV001576378 | pathogenic | Retinitis pigmentosa 12; Leber congenital amaurosis 8 | 2022-02-10 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 480 of the CRB1 protein (p.Cys480Ser). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individuals with Leber congenital amaurosis or retinitis pigmentosa (PMID: 23847139; Invitae). ClinVar contains an entry for this variant (Variation ID: 1067463). 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. This variant disrupts the p.Cys480 amino acid residue in CRB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11231775, 21757580, 23847139). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |