Submissions for variant NM_201253.3(CRB1):c.4121_4130del (p.Ala1374fs)

dbSNP: rs281865175

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV000086353	SCV002019730	pathogenic	not provided	2021-05-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001851689	SCV002219467	pathogenic	Retinitis pigmentosa 12; Leber congenital amaurosis 8	2024-03-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ala1374Glufs*20) in the CRB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 33 amino acid(s) of the CRB1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with inherited retinal dystrophy (PMID: 12567265). It has also been observed to segregate with disease in related individuals. This variant is also known as del 4121–4130. ClinVar contains an entry for this variant (Variation ID: 5740). This variant disrupts a region of the CRB1 protein in which other variant(s) (p.Arg1390*) have been determined to be pathogenic (PMID: 23379534, 29068479). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000006096	SCV004180911	pathogenic	Leber congenital amaurosis 8	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000006095	SCV004180912	pathogenic	Retinitis pigmentosa 12	2023-04-11	criteria provided, single submitter	clinical testing
OMIM	RCV000006095	SCV000026277	pathogenic	Retinitis pigmentosa 12	2009-02-15	no assertion criteria provided	literature only
OMIM	RCV000006096	SCV000026278	pathogenic	Leber congenital amaurosis 8	2009-02-15	no assertion criteria provided	literature only
Retina International	RCV000086353	SCV000118499	not provided	not provided		no assertion provided	not provided
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001003001	SCV001161055	pathogenic	Leber congenital amaurosis	2019-06-23	no assertion criteria provided	research
Laboratory of Genetics in Ophthalmology, Institut Imagine	RCV000006096	SCV001425494	pathogenic	Leber congenital amaurosis 8		no assertion criteria provided	research