ClinVar Miner

Submissions for variant NM_201253.3(CRB1):c.3221T>C (p.Leu1074Ser)

gnomAD frequency: 0.00001  dbSNP: rs751303205
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001885124 SCV002240803 pathogenic Retinitis pigmentosa 12; Leber congenital amaurosis 8 2023-11-01 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1074 of the CRB1 protein (p.Leu1074Ser). This variant is present in population databases (rs751303205, gnomAD 0.01%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 22219627, 28559085; Invitae). 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: 1319944). 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%. For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein RCV001771820 SCV002011771 uncertain significance Pigmented paravenous retinochoroidal atrophy 2021-08-18 no assertion criteria provided clinical testing

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