ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.1913C>T (p.Ser638Leu)

gnomAD frequency: 0.00002  dbSNP: rs267598278
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001854256 SCV002237805 pathogenic Retinitis pigmentosa 12; Leber congenital amaurosis 8 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 638 of the CRB1 protein (p.Ser638Leu). This variant is present in population databases (rs267598278, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of CRB1-related conditions (PMID: 28041643, 33576794, 33633436). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 73455). 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 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Dept Of Ophthalmology, Nagoya University RCV000505040 SCV004705153 likely pathogenic Retinal dystrophy 2023-10-01 criteria provided, single submitter research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000505040 SCV000598911 likely pathogenic Retinal dystrophy 2015-01-01 no assertion criteria provided research

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