ClinVar Miner

Submissions for variant NM_001297.5(CNGB1):c.413-1G>A (rs189234741)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000504965 SCV000914732 likely pathogenic Retinitis pigmentosa 2018-10-18 criteria provided, single submitter clinical testing The CNGB1 c.413-1G>A variant has been reported in three studies in at least four probands with retinitis pigmentosa, all in a homozygous state (Azam et al. 2011; Saqib et al. 2015; van Huet et al. 2015). Two of these probands were siblings and their unaffected parents were shown to carry the variant in a heterozygous state. Control data are not available for this variant which is reported at a frequency of 0.00024 in the South Asian population from the Exome Aggregation Consortium. When this variant was incorporated into a vector which was transfected into HeLa cells and retrotranscribed, the cDNA demonstrated a frameshift and introduction of a premature stop codon (Saqib et al. 2015). Based on the evidence and due to the potential impact of splice acceptor variants, the c.413-1G>A variant is classified as likely pathogenic for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV001056559 SCV001221009 pathogenic not provided 2019-12-10 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 6 of the CNGB1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs189234741, ExAC 0.02%). This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 25943428). It has also been observed to segregate with disease in related individuals. This variant is also known as IVS6-1G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 437976). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 25943428). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CNGB1 are known to be pathogenic (PMID: 15557452, 24043777). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074746 SCV001240341 pathogenic Retinal dystrophy 2019-05-16 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504965 SCV000598716 pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Human Genetics - Radboudumc,Radboudumc RCV000678544 SCV000804622 pathogenic Retinitis pigmentosa 45 2016-09-01 no assertion criteria provided clinical testing
Sharon lab,Hadassah-Hebrew University Medical Center RCV000504965 SCV001161025 pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research

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