Submissions for variant NM_025114.4(CEP290):c.1666del (p.Ile556fs)

dbSNP: rs727503855

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
UW Hindbrain Malformation Research Program, University of Washington	RCV000201771	SCV000256368	pathogenic	Joubert syndrome 5	2015-02-23	criteria provided, single submitter	research
Invitae	RCV000697843	SCV000826475	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis	2023-12-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile556Phefs*17) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individuals with Joubert syndrome (PMID: 26047050, 26092869, 27491411). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217622). For these reasons, this variant has been classified as Pathogenic.
Mendelics	RCV000988888	SCV001138786	pathogenic	Joubert syndrome 1	2019-05-28	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001075310	SCV001240928	pathogenic	Retinal dystrophy	2017-12-29	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268720	SCV001447853	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV001376373	SCV001573491	pathogenic	Leber congenital amaurosis 10	2021-04-08	criteria provided, single submitter	research	The CEP290 c.1666del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PS3. Based on this evidence we have classified this variant as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV002500629	SCV002811713	pathogenic	Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14	2021-08-19	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001268720	SCV003820650	pathogenic	not provided	2022-01-02	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003468916	SCV004214856	pathogenic	Bardet-Biedl syndrome 14	2023-10-18	criteria provided, single submitter	clinical testing
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001002938	SCV001160973	pathogenic	Leber congenital amaurosis	2019-06-23	no assertion criteria provided	research
Natera, Inc.	RCV001002938	SCV001457923	pathogenic	Leber congenital amaurosis	2020-09-16	no assertion criteria provided	clinical testing