Submissions for variant NM_201253.3(CRB1):c.455G>A (p.Cys152Tyr)

dbSNP: rs1571848744

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001074569	SCV001240160	pathogenic	Retinal dystrophy	2018-12-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001377780	SCV001575203	pathogenic	Retinitis pigmentosa 12; Leber congenital amaurosis 8	2023-12-28	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 152 of the CRB1 protein (p.Cys152Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 23449718, 25356976). 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: 812296). 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 95%. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV003455044	SCV004178821	likely pathogenic	Leber congenital amaurosis 8	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003455043	SCV004178822	likely pathogenic	Retinitis pigmentosa 12	2023-04-11	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001002988	SCV001161042	likely pathogenic	Leber congenital amaurosis	2019-06-23	no assertion criteria provided	research