Submissions for variant NM_201253.3(CRB1):c.2308G>A (p.Gly770Ser)

gnomAD frequency: 0.00003  dbSNP: rs767648174

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001069480	SCV001234648	pathogenic	Retinitis pigmentosa 12; Leber congenital amaurosis 8	2024-01-27	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 770 of the CRB1 protein (p.Gly770Ser). This variant is present in population databases (rs767648174, gnomAD 0.007%). This missense change has been observed in individual(s) with early-onset severe retinal dystrophy and/or retinitis pigmentosa (PMID: 27113771, 27208204, 28559085, 30576320). 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: 236478). 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.
Blueprint Genetics	RCV000225453	SCV001240763	likely pathogenic	Retinal dystrophy	2018-10-05	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376283	SCV001573371	likely pathogenic	Retinitis pigmentosa 12	2021-04-08	criteria provided, single submitter	research	The CRB1 c.2308G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM1, PM3-S. Based on this evidence we have classified this variant as Likely Pathogenic.
Genome-Nilou Lab	RCV003454681	SCV004180037	likely pathogenic	Leber congenital amaurosis 8	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003454682	SCV004180038	likely pathogenic	Pigmented paravenous retinochoroidal atrophy	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001376283	SCV004180039	likely pathogenic	Retinitis pigmentosa 12	2023-04-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003454681	SCV004211140	pathogenic	Leber congenital amaurosis 8	2024-03-19	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV000225453	SCV004706097	pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV000225453	SCV000282584	uncertain significance	Retinal dystrophy		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001833240	SCV002090174	pathogenic	Leber congenital amaurosis	2020-08-25	no assertion criteria provided	clinical testing