ClinVar Miner

Submissions for variant NM_001257965.1(CRB1):c.291_299delAATTGATGG (p.Ile98_Gly100del) (rs398124615)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000082822 SCV000114870 likely benign not specified 2013-09-25 criteria provided, single submitter clinical testing
GeneDx RCV000598962 SCV000709902 pathogenic not provided 2018-07-16 criteria provided, single submitter clinical testing The c.498_506delAATTGATGG variant in the CRB1 gene has been reported previously in association with autosomal recessive early-onset retinal dystrophies when present in the homozygous state or when in trans with another disease-causing variant (Corton et al., 2013). The c.498_506delAATTGATGG variant causes an in-frame deletion of 3 amino acid residues, denoted p.Ile167_Gly169del. The c.498_506delAATTGATGG variant is observed in 11/10150 (0.1%) alleles from individuals of Ashkenazi Jewish background, including 1 homozygous individual in large population cohorts (Lek et al., 2016). We interpret c.498_506delAATTGATGG as a pathogenic variant.
Human Genetics - Radboudumc,Radboudumc RCV000505172 SCV000804629 pathogenic Macular dystrophy 2016-09-01 no assertion criteria provided clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000778208 SCV000914374 pathogenic CRB1-Related Disorders 2018-08-09 criteria provided, single submitter clinical testing The CRB1 c.498_506delAATTGATGG (p.Ile167_Gly169del) variant is an inframe deletion that has been reported in at least five studies in which it is identified in a total of 10 individuals, including in one in a homozygous state and in nine in a compound heterozygous state, and in three additional alleles (Corton et al. 2013; Zaneveld et al. 2015; Sergouniotis et al. 2016; Carss et al. 2017; Shah et al. 2017). Individuals with the variant present with a range of phenotypes including early-onset retinitis pigmentosa, Stargardt macular dystrophy, isolated maculopathy, macular dystrophy, and retinal dystrophy. No individuals with the variant have been reported with Leber congenital amaurosis or pigmented paravenous chorioretinal atrophy. Control data are unavailable for this variant, which is reported at a frequency of 0.00108 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the collective evidence, the p.Ile167_Gly169del variant is classified as pathogenic for CRB1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000615750 SCV000731981 likely pathogenic Retinal dystrophy 2017-11-29 criteria provided, single submitter clinical testing The p.Ile98_Gly100del (NM_001257965.1 c.291_299delAATTGATGG) variant in CRB1 (also reported as NM_201253.2:p.Ile167_Gly169del) has been previously reported in 1 homozygous and 7 compound heterozygous individuals with retinal disorders including retinal dystrophy, retinitis pigmentosa, and familial foveal retinoschisis (Corton 2013, Vincent 2016, Riera 2017). It has also been identified in 0.1% (124/126,500) of European chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP rs748136623). This variant is a deletion of 3 amino acids at position 98-100, and it is unclear if this deletion will impact the protein. In summary, although additional studies are required to fully establish its clinical significance, the p.Ile98_Gly100del variant is likely pathogenic for retinal disorders based on its biallelic occurrence individuals with these diseases. ACMG/AMP Criteria applied: PM3 (upgraded to Strong based on multiple occurrences), PM4 (Richards 2015).
Molecular Medicine,University of Leeds RCV000505172 SCV000611552 pathogenic Macular dystrophy 2017-10-27 criteria provided, single submitter research
NIHR Bioresource Rare Diseases,University of Cambridge RCV000505172 SCV000598923 likely pathogenic Macular dystrophy 2015-01-01 no assertion criteria provided research

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