Submissions for variant NM_020366.4(RPGRIP1):c.895_896del (p.Glu299fs)

dbSNP: rs1594180177

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	RCV001005021	SCV001164586	pathogenic	Leber congenital amaurosis 6	2018-12-03	criteria provided, single submitter	research	The heterozygous p.Glu299SerfsTer21 variant in RPGRIP1 was identified by our study in the compound heterozygous state, with another likely pathogenic variant, in one individual with Leber congenital amaurosis. The presence of this variant in combination with a likely pathogenic variant and in an individual with Leber congenital amaurosis slightly increases the likelihood that the p.Glu299SerfsTer21 variant is pathogenic. The p.Glu299SerfsTer21 variant in RPGRIP1 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 299 and leads to a premature termination codon 21 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the RPGRIP1 gene is an established disease mechanism in autosomal recessive Leber congenital amaurosis. In summary, the clinical significance of the p.Glu299SerfsTer21 variant is pathogenic. Criteria applied: PM2, PVS1, PM3_Supporting (Richards 2015).
Laboratory of Genetics in Ophthalmology, Institut Imagine	RCV001005021	SCV001438575	pathogenic	Leber congenital amaurosis 6		no assertion criteria provided	research