Submissions for variant NM_020366.4(RPGRIP1):c.3565C>T (p.Arg1189Ter)

gnomAD frequency: 0.00001  dbSNP: rs752175052

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000428349	SCV000521210	pathogenic	not provided	2017-01-09	criteria provided, single submitter	clinical testing	The R1189X variant in the RPGRIP1 gene has been reported previously with unspecified zygosity in two unrelated individuals with familial non-syndromic cone-rod dystrophy (Patel et al., 2016) and in the homozygous state in three unrelated patients with Leber congenital amaurosis (Abu-Safieh et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R1189X variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R1189X as a pathogenic variant.
Invitae	RCV001387165	SCV001587724	pathogenic	Cone-rod dystrophy 13; Leber congenital amaurosis 6	2020-01-20	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RPGRIP1 are known to be pathogenic (PMID: 11528500, 23105016). This variant has been observed in individual(s) with retinal dystrophies (PMID: 23105016, 24123792, 26355662). ClinVar contains an entry for this variant (Variation ID: 381684). This variant is present in population databases (rs752175052, ExAC 0.006%). This sequence change creates a premature translational stop signal (p.Arg1189*) in the RPGRIP1 gene. It is expected to result in an absent or disrupted protein product.
Genome-Nilou Lab	RCV001261193	SCV002045275	pathogenic	Leber congenital amaurosis 6	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001800668	SCV002045286	pathogenic	Cone-rod dystrophy 13	2021-11-07	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000428349	SCV004238123	pathogenic	not provided	2023-07-20	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001261193	SCV004804929	pathogenic	Leber congenital amaurosis 6	2024-03-17	criteria provided, single submitter	research
Laboratory of Genetics in Ophthalmology, Institut Imagine	RCV001261193	SCV001438594	pathogenic	Leber congenital amaurosis 6		no assertion criteria provided	research