ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.2290C>T (p.Arg764Cys)

gnomAD frequency: 0.00004  dbSNP: rs62635654
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Total submissions: 24
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Medicine, University of Leeds RCV000656137 SCV000611556 pathogenic Macular dystrophy 2017-10-27 criteria provided, single submitter research
Invitae RCV001052374 SCV001216583 pathogenic Retinitis pigmentosa 12; Leber congenital amaurosis 8 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 764 of the CRB1 protein (p.Arg764Cys). This variant is present in population databases (rs62635654, gnomAD 0.01%). This missense change has been observed in individual(s) with CRB1-related retinopathy (PMID: 10508521, 11389483, 12700176, 20956273, 24512366, 26047050, 28129017, 28341475). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5732). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074882 SCV001240486 pathogenic Retinal dystrophy 2019-08-12 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000086317 SCV001248712 pathogenic not provided 2018-07-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000086317 SCV001446685 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Institute of Medical Molecular Genetics, University of Zurich RCV001352991 SCV001548082 likely pathogenic CRB1-related maculopathy 2021-01-30 criteria provided, single submitter clinical testing
Genomics England Pilot Project, Genomics England RCV000006086 SCV001759998 likely pathogenic Retinitis pigmentosa 12 criteria provided, single submitter clinical testing
GeneDx RCV000086317 SCV001830805 pathogenic not provided 2022-03-09 criteria provided, single submitter clinical testing 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: 28129017, 10508521, 20956273, 24512366, 26047050, 27670293, 28341475, 23379534, 29391521, 28559085, 31980526, 31630094, 31589614, 34884448, 31736247, 34426522, 33969091, 34946856, 33546218, 30718709, 32507488)
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000787577 SCV001950247 likely pathogenic Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The p.Arg764Cys variant in CRB1 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, BP4, PP1-M, PM3. Based on this evidence we have classified this variant as Likely Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
Fulgent Genetics, Fulgent Genetics RCV002496279 SCV002810757 pathogenic Pigmented paravenous retinochoroidal atrophy; Retinitis pigmentosa 12; Leber congenital amaurosis 8 2021-07-01 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003447471 SCV004175772 pathogenic Retinitis pigmentosa-deafness syndrome 2023-03-01 criteria provided, single submitter clinical testing The missense variant c.2290C>T (p.Arg764Cys) in the CRB1 gene has been reported previously in a compound heterozygous and homozygous state in individuals affected with Autosomal recessive retinitis pigmentosa. Experimental studies have shown that this missense change affects protein function (den Hollander et al., 1999; Yang et al., 2016). This variant is reported with the allele frequency (0.007%) in the gnomAD and novel in the 1000 genome database. It is submitted to ClinVar with varying interpretations as Pathogenic/ Likely Pathogenic. The amino acid Arginine at position 764 is changed to a Cysteine changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted as damaging by SIFT. The amino acid change p.Arg764Cys in CRB1 is predicted as conserved by PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV001250604 SCV004180027 likely pathogenic Leber congenital amaurosis 8 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003450615 SCV004180028 likely pathogenic Pigmented paravenous retinochoroidal atrophy 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000006086 SCV004180029 likely pathogenic Retinitis pigmentosa 12 2023-04-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV001250604 SCV004211120 pathogenic Leber congenital amaurosis 8 2023-10-16 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000086317 SCV004238130 likely pathogenic not provided 2023-08-09 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004540990 SCV004774970 pathogenic CRB1-related disorder 2023-12-05 criteria provided, single submitter clinical testing The CRB1 c.2290C>T variant is predicted to result in the amino acid substitution p.Arg764Cys. This variant has been documented to be causative for autosomal recessive retinitis pigmentosa (RP) and autosomal recessive Leber congenital amaurosis (den Hollander et al. 1999. PubMed ID: 10508521; Wang et al. 2015. PubMed ID: 26047050; Corton et al. 2013. PubMed ID: 23379534).
OMIM RCV000006086 SCV000026268 pathogenic Retinitis pigmentosa 12 1999-10-01 no assertion criteria provided literature only
Retina International RCV000086317 SCV000118463 not provided not provided no assertion provided not provided
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet RCV000787577 SCV000926557 pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Laboratory of Genetics in Ophthalmology, Institut Imagine RCV001250604 SCV001425472 pathogenic Leber congenital amaurosis 8 no assertion criteria provided research
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000086317 SCV001958962 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000086317 SCV001966364 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein RCV001250604 SCV002583351 pathogenic Leber congenital amaurosis 8 2021-12-01 no assertion criteria provided clinical testing

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