ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.3307G>A (p.Gly1103Arg) (rs62636275)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000086341 SCV000321519 pathogenic not provided 2018-03-30 criteria provided, single submitter clinical testing The G1103R variant has been published as a pathogenic variant, including an extended family where it segregated with disease and in several cases with another pathogenic variant in the CRB1 gene (Hanein et al., 2004; Bujakowska et al., 2012; Beryozkin et al., 2013; Benayoun et al., 2009; Srilekha et al., 2015; Watson et al., 2014). The G1103R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The G1103R 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. In summary, based on the currently available information, this variant is pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000086341 SCV000339784 pathogenic not provided 2016-04-01 criteria provided, single submitter clinical testing
Invitae RCV000648818 SCV000770639 pathogenic Retinitis pigmentosa 12; Leber congenital amaurosis 8 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1103 of the CRB1 protein (p.Gly1103Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs62636275, ExAC 0.006%). This variant has been reported in the literature in individuals affected with Leber congenital amaurosis (LCA) or pigment epithelium (PR), either in a homozygous status (PMID: 20079931, 23449718) or in a combination of the second alleles in CRB1 (PMID: 15024725, 20956273, 22065545, 25133751). It has also been found to segregate with LCA or PR in several families (PMID: 26147992, 16543197, 19140180). A haplotype analysis revealed this missense change as a founder mutation in the Israeli and Palestinian populations (PMID: 23449718). ClinVar contains an entry for this variant (Variation ID: 5739). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073404 SCV001238945 pathogenic Retinal dystrophy 2019-01-22 criteria provided, single submitter clinical testing
OMIM RCV000006093 SCV000026275 pathogenic Leber congenital amaurosis 8 2009-02-15 no assertion criteria provided literature only
OMIM RCV000006094 SCV000026276 pathogenic Retinitis pigmentosa 12 2009-02-15 no assertion criteria provided literature only
Retina International RCV000086341 SCV000118487 not provided not provided no assertion provided not provided
Institute for Ophthalmic Research,University Tuebingen RCV000786009 SCV000924649 pathogenic Early-onset retinal dystrophy 2017-12-13 no assertion criteria provided research
Sharon lab,Hadassah-Hebrew University Medical Center RCV001002998 SCV001161052 pathogenic Leber congenital amaurosis 2019-06-23 no assertion criteria provided research
Laboratory of Genetics in Ophthalmology,Institut Imagine RCV000006093 SCV001425486 pathogenic Leber congenital amaurosis 8 no assertion criteria provided research
Natera, Inc. RCV001002998 SCV001460950 pathogenic Leber congenital amaurosis 2020-09-16 no assertion criteria provided clinical testing

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