Submissions for variant NM_201253.3(CRB1):c.2230C>T (p.Arg744Ter)

dbSNP: rs150412614

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001075564	SCV001241191	pathogenic	Retinal dystrophy	2019-01-03	criteria provided, single submitter	clinical testing
Institute of Medical Molecular Genetics, University of Zurich	RCV001250600	SCV001548135	likely pathogenic	Leber congenital amaurosis 8	2021-01-30	criteria provided, single submitter	clinical testing
3billion	RCV001250600	SCV002059077	pathogenic	Leber congenital amaurosis 8	2022-01-03	criteria provided, single submitter	clinical testing	Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000635155, PMID:25323024, 3billion dataset). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000012, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001869175	SCV002240654	pathogenic	Retinitis pigmentosa 12; Leber congenital amaurosis 8	2022-02-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg744*) in the CRB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CRB1 are known to be pathogenic (PMID: 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521). This variant is present in population databases (rs150412614, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with inherited retinal dystrophy (PMID: 25323024, 31456290, 31896775, 33342761). ClinVar contains an entry for this variant (Variation ID: 635155). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV001250600	SCV004180015	pathogenic	Leber congenital amaurosis 8	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003453620	SCV004180016	pathogenic	Pigmented paravenous retinochoroidal atrophy	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003453619	SCV004180017	pathogenic	Retinitis pigmentosa 12	2023-04-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001250600	SCV004211174	pathogenic	Leber congenital amaurosis 8	2024-03-07	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV001075564	SCV004705186	pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Molecular Genetics Laboratory, Institute for Ophthalmic Research	RCV000786007	SCV000924647	pathogenic	Early-onset retinal dystrophy	2017-12-13	no assertion criteria provided	research
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001002994	SCV001161048	pathogenic	Leber congenital amaurosis	2019-06-23	no assertion criteria provided	research
Laboratory of Genetics in Ophthalmology, Institut Imagine	RCV001250600	SCV001425468	pathogenic	Leber congenital amaurosis 8		no assertion criteria provided	research