ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.135C>G (p.Cys45Trp)

gnomAD frequency: 0.00035  dbSNP: rs145141811
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487047 SCV000564914 uncertain significance not provided 2016-03-12 criteria provided, single submitter clinical testing The C45W variant in the CRB1 gene has been reported previously in the heterozygous state in two individuals with retinitis pigmentosa in whom a second CRB1 pathogenic variant was not identified (Clark et al., 2010; Neveling et al., 2012). The C45W variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common variant in these populations. The C45W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret C45W as a variant of uncertain significance.
Illumina Laboratory Services, Illumina RCV000787828 SCV001257167 uncertain significance Retinitis pigmentosa 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001247776 SCV001421219 uncertain significance Retinitis pigmentosa 12; Leber congenital amaurosis 8 2022-10-18 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 45 of the CRB1 protein (p.Cys45Trp). This variant is present in population databases (rs145141811, gnomAD 0.07%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 20591486, 22164218, 30718709). ClinVar contains an entry for this variant (Variation ID: 418147). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV003449162 SCV004178802 uncertain significance Leber congenital amaurosis 8 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449163 SCV004178803 uncertain significance Pigmented paravenous retinochoroidal atrophy 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449161 SCV004178804 uncertain significance Retinitis pigmentosa 12 2023-04-11 criteria provided, single submitter clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet RCV000787828 SCV000926841 likely pathogenic Retinitis pigmentosa 2018-04-01 flagged submission research
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001252198 SCV001427949 uncertain significance Intellectual disability 2019-01-01 no assertion criteria provided clinical testing
Natera, Inc. RCV001275643 SCV001460933 uncertain significance Leber congenital amaurosis 2020-09-16 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000487047 SCV001923924 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000487047 SCV001959888 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000487047 SCV001968756 uncertain significance not provided no assertion criteria provided clinical testing

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