ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.2300T>C (p.Leu767Pro)

gnomAD frequency: 0.00001  dbSNP: rs1451348539
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001042149 SCV001205815 pathogenic Retinitis pigmentosa 12; Leber congenital amaurosis 8 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 767 of the CRB1 protein (p.Leu767Pro). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individuals with Leber congenital amaurosis or retinitis pigmentosa (PMID: 17964524; Invitae). ClinVar contains an entry for this variant (Variation ID: 840207). 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 95%. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074779 SCV001240375 pathogenic Retinal dystrophy 2019-06-23 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003455171 SCV004180030 pathogenic Leber congenital amaurosis 8 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003455172 SCV004180031 pathogenic Pigmented paravenous retinochoroidal atrophy 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003455170 SCV004180032 pathogenic Retinitis pigmentosa 12 2023-04-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV003455171 SCV004211121 likely pathogenic Leber congenital amaurosis 8 2023-12-04 criteria provided, single submitter clinical testing
GeneDx RCV004768801 SCV005376511 uncertain significance not provided 2024-04-15 criteria provided, single submitter clinical testing Observed in apparent homozygous state in patients with Leber congenital amaurosis in the literature and not observed in homozygous state in controls (PMID: 29343940, 17964524); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17964524, 31964843, 29343940, 35243176)
Natera, Inc. RCV001827256 SCV002090171 likely pathogenic Leber congenital amaurosis 2020-06-08 no assertion criteria provided clinical testing

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