ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.2555T>C (p.Ile852Thr) (rs62636271)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000529725 SCV000650636 pathogenic Retinitis pigmentosa 12; Leber congenital amaurosis 8 2017-03-16 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 852 of the CRB1 protein (p.Ile852Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (rs62636271, ExAC no frequency). This variant has been reported to segregate with Leber congenital amaurosis in two families (PMID: 17724218, 26872607). In one of these families, all three affected siblings were homozygous for this variant. This variant has also been observed to occur with a Likely Pathogenic variant (c.4005+1G>A) in CRB1 in an individual with Leber congenital amaurosis (PMID: 15024725). While it is unknown if these two variants are on the same or opposite chromosomes, this observation suggests the c.2555T>C substitution may contribute to the cause of disease. ClinVar contains an entry for this variant (Variation ID: 99883). 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. For these reasons, this variant has been classified as Pathogenic.
Retina International RCV000086323 SCV000118469 not provided not provided no assertion provided not provided
Sharon lab,Hadassah-Hebrew University Medical Center RCV001002996 SCV001161050 likely pathogenic Leber congenital amaurosis 2019-06-23 no assertion criteria provided research
Laboratory of Genetics in Ophthalmology,Institut Imagine RCV001250658 SCV001425529 pathogenic Leber congenital amaurosis 8 no assertion criteria provided research

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