Submissions for variant NM_201253.3(CRB1):c.2309G>A (p.Gly770Asp)

dbSNP: rs878853365

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003323464	SCV004029977	uncertain significance	not specified	2023-07-10	criteria provided, single submitter	clinical testing	Variant summary: CRB1 c.2309G>A (p.Gly770Asp) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250752 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2309G>A has been reported in the literature in at least one compound heterozygous individual affected with Retinal Dystrophy (e.g., Ellingford_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 27208204). No submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. Additionally, another missense variant impacting the same codon, c.2308G>A (p.G770S), has been reported in the literature in patients affected with retinal dystrophy (PMIDs: 27208204, 30576320, 31879567) and reported as pathogenic in ClinVar. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals	RCV000225667	SCV000282577	uncertain significance	Retinal dystrophy		no assertion criteria provided	clinical testing