Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001232801 | SCV001405370 | pathogenic | Retinitis pigmentosa 12; Leber congenital amaurosis 8 | 2022-07-12 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Leber congenital amaurosis or retinitis pigmentosa (PMID: 16936081; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 CRB1 protein function. ClinVar contains an entry for this variant (Variation ID: 959447). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 753 of the CRB1 protein (p.Leu753Pro). |
| Gene |
RCV001779138 | SCV002015417 | uncertain significance | not provided | 2021-05-11 | 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; Identified in an individual with Leber Congenital Amaurosis in published literature who also harbored a second CRB1 variant, presumably in trans; this individual's similarly affected siblings and mother with markedly abnormal mfERG findings in one eye were heterozygous for the L753P variant and did not harbor the second CRB1 variant identified in the proband (Yzer et al., 2006); This variant is associated with the following publications: (PMID: 15691574, 16936081) |
| Institute of Human Genetics, |
RCV004813938 | SCV005069863 | uncertain significance | Retinal dystrophy | 2021-01-01 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005012649 | SCV005636281 | likely pathogenic | Pigmented paravenous retinochoroidal atrophy; Retinitis pigmentosa 12; Leber congenital amaurosis 8 | 2024-01-04 | criteria provided, single submitter | clinical testing |