Submissions for variant NM_020366.4(RPGRIP1):c.1753C>T (p.Pro585Ser)

gnomAD frequency: 0.00155  dbSNP: rs147586703

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000325954	SCV000336115	uncertain significance	not provided	2017-04-17	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763912	SCV000894853	uncertain significance	Cone-rod dystrophy 13; Leber congenital amaurosis 6	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000325954	SCV000971068	likely benign	not provided	2018-06-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000763912	SCV001098300	likely benign	Cone-rod dystrophy 13; Leber congenital amaurosis 6	2024-01-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001111169	SCV001268692	likely benign	Leber congenital amaurosis 6	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Genome-Nilou Lab	RCV001111169	SCV002045878	likely benign	Leber congenital amaurosis 6	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001800646	SCV002045889	likely benign	Cone-rod dystrophy 13	2021-11-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002282101	SCV002570919	likely benign	not specified	2022-07-14	criteria provided, single submitter	clinical testing	Variant summary: RPGRIP1 c.1753C>T (p.Pro585Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 248042 control chromosomes, predominantly at a frequency of 0.0028 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in RPGRIP1 causing Leber Congenital Amaurosis phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.1753C>T has been reported in the literature in individuals affected with Leber Congenital Amaurosis, Primary Open-Angle Glaucoma or Retinitis Pigmentosa (Wiszniewski_2010, Fernndez-Martnez_2011, Ge_2015, Wang_2017). These reports do not provide unequivocal conclusions about association of the variant with Leber Congenital Amaurosis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=2) and likely benign (n=4). Based on the evidence outlined above, the variant was classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000325954	SCV005330146	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	RPGRIP1: BP4, BS2
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000325954	SCV001800475	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000325954	SCV001918811	likely benign	not provided		no assertion criteria provided	clinical testing