Submissions for variant NM_201253.3(CRB1):c.2549_2552del (p.Gly850fs)

dbSNP: rs62636270

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001004993	SCV001164551	likely pathogenic	Leber congenital amaurosis 8	2018-12-03	criteria provided, single submitter	research	The heterozygous p.Gly850ValfsTer5 variant in CRB1 was identified by our study in the compound heterozygous state, confirmed in trans with a likely pathogenic variant, in two siblings with Leber congenital amaurosis. The p.Gly850ValfsTer5 variant in CRB1 has not been previously reported in individuals with Leber Congenital Amaurosis and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 850 and leads to a premature termination codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the CRB1 gene is an established disease mechanism for Leber Congenital Amaurosis. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. Criteria applied: PM2, PVS1 (Richards 2015).
Retina International	RCV000086322	SCV000118468	not provided	not provided		no assertion provided	not provided