ClinVar Miner

Submissions for variant NM_019098.4(CNGB3):c.886_896delinsT (p.Thr296fs) (rs886063161)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000278041 SCV000475220 likely pathogenic CNGB3-Related Disorders 2017-04-28 criteria provided, single submitter clinical testing The CNGB3 c.886_896delACTTCTACAAAinsT (p.Thr296TyrfsTer9) variant is a frameshift variant that is predicted to result in premature termination of the protein. The variant has been reported in a total of seven individuals with achromatopsia, including six who were compound heterozygous for the variant and one who was heterozygous without a second identified variant (Kohl et al. 2005). The variant has not been reported in association with Stargardt disease, though Thiadens et al. (2010) reported two unrelated individuals with autosomal recessive progressive cone dystrophy who were both compound heterozygous for the p.Thr296TyrfsTer9 variant and a second null variant. An unaffected parent and an unaffected child of one of the individuals were both heterozygous. The p.Thr296TyrfsTer9 variant was absent from 100 controls and is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium. Based on the evidence from the literature and the potential impact of frameshift variants, the p.Thr296TyrfsTer9 variant is classified as pathogenic for CNGB3-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000821438 SCV000962193 pathogenic not provided 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr296Tyrfs*9) in the CNGB3 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in several individuals affected with achromatopsia (PMID: 23362848, 15657609, 20079539). ClinVar contains an entry for this variant (Variation ID: 363876). Loss-of-function variants in CNGB3 are known to be pathogenic (PMID: 15657609). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000821438 SCV001167866 pathogenic not provided 2019-01-21 criteria provided, single submitter clinical testing The c.886_896del11insT variant in the CNGB3 gene has been reported previously in association with achromatopsia and progressive cone dystrophy (Thiadens et al., 2010; Kohl et al., 2005). This variant causes a frameshift starting with codon Threonine 296, changes this amino acid to a Tyrosine residue, and creates a premature Stop codon at position 9 of the new reading frame, denoted p.Thr296TyrfsX9. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.886_896del11insT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.886_896del11insT as a pathogenic variant.
Institute for Ophthalmic Research,University Tuebingen RCV000497907 SCV000575787 pathogenic Achromatopsia 3 2017-03-27 no assertion criteria provided research

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