Submissions for variant NM_020366.4(RPGRIP1):c.1107del (p.Glu370fs)

dbSNP: rs61751266

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001047199	SCV001211139	pathogenic	Cone-rod dystrophy 13; Leber congenital amaurosis 6	2024-08-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu370Asnfs*5) in the RPGRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPGRIP1 are known to be pathogenic (PMID: 11528500, 23105016). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis (PMID: 11283794, 20079931, 24997176, 30202406). This variant is also known as Lys342(1-bp del). ClinVar contains an entry for this variant (Variation ID: 99809). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Centogene AG - the Rare Disease Company	RCV000171128	SCV001426643	pathogenic	Leber congenital amaurosis 6		criteria provided, single submitter	clinical testing
DBGen Ocular Genomics	RCV000171128	SCV001815997	pathogenic	Leber congenital amaurosis 6	2021-06-23	criteria provided, single submitter	clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000171128	SCV001984513	pathogenic	Leber congenital amaurosis 6	2020-04-07	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000086238	SCV002019890	pathogenic	not provided	2021-02-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000171128	SCV002044747	pathogenic	Leber congenital amaurosis 6	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001800395	SCV002044758	pathogenic	Cone-rod dystrophy 13	2021-11-07	criteria provided, single submitter	clinical testing
3billion	RCV000171128	SCV002058264	pathogenic	Leber congenital amaurosis 6	2023-11-22	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.006%). Predicted Consequence/Location: Missense variant In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.90; 3Cnet: 0.90). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000436090 /PMID: 28041643 /3billion dataset).A different missense change at the same codon (p.Gly780Ser) has been reported to be associated with OCA2 related disorder (PMID: 32741191). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001800395	SCV002818118	pathogenic	Cone-rod dystrophy 13	2024-10-04	criteria provided, single submitter	research	PVS1, PM2, PP4
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000171128	SCV004806819	pathogenic	Leber congenital amaurosis 6	2024-03-26	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000171128	SCV005088877	pathogenic	Leber congenital amaurosis 6	2021-02-13	criteria provided, single submitter	clinical testing	This variant has been observed in homozygous state in multiple individuals with a clinical diagnosis of Leber congenital amaurosis [PMID: 30202406, 20079931, 24997176] and it was previously reported as recurrent variant (represented as c.1007delA (p.Glu370Asnfs*5) in the article [PMID: 24997176].
OMIM	RCV000171128	SCV000025451	pathogenic	Leber congenital amaurosis 6	2001-05-01	no assertion criteria provided	literature only
Retina International	RCV000086238	SCV000118384	not provided	not provided		no assertion provided	not provided
Molecular Genetics Laboratory, Institute for Ophthalmic Research	RCV000786015	SCV000924655	pathogenic	Leber congenital amaurosis	2017-12-13	no assertion criteria provided	research
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000171128	SCV001133096	pathogenic	Leber congenital amaurosis 6	2019-09-26	no assertion criteria provided	clinical testing
Laboratory of Genetics in Ophthalmology, Institut Imagine	RCV000171128	SCV001438576	pathogenic	Leber congenital amaurosis 6		no assertion criteria provided	research