ClinVar Miner

Submissions for variant NM_001297.5(CNGB1):c.2957A>T (p.Asn986Ile) (rs201162411)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000153040 SCV000202494 uncertain significance not provided 2014-04-27 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000504912 SCV000398309 pathogenic Retinitis pigmentosa 2017-08-25 criteria provided, single submitter clinical testing The CNGB1 c.2957A>T (p.Asn986Ile) missense variant has been reported in two studies in which it is found in six unrelated individuals with an autosomal recessive form of retinitis pigmentosa, including in four in a homozygous state and in two in a compound heterozygous state (Simpson et al. 2011; Hull et al. 2017). Common phenotypes in these individuals included night blindness with an onset in infancy or childhood, loss of peripheral vision in adulthood, and based on a fundus exam, a majority of patients had optic disc pallor, retinal pigment epithelium atrophy, and intraretinal pigment migration. The two individuals with the variant in a compound heterozygous state also had affected siblings with the same variants, one affected sister in one family and an additional affected brother and sister in the second family (Hull et al. 2017). The p.Asn986Ile variant was absent from 720 control chromosomes (Simpson et al. 2011) and is reported at a frequency of 0.00652 in the European (Finnish) population of the Genome Aggregation Database. Based on the clinical evidence, the p.Asn986Ile variant is classified as pathogenic for an autosomal recessive form of retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000153040 SCV001207500 pathogenic not provided 2020-01-02 criteria provided, single submitter clinical testing This sequence change replaces asparagine with isoleucine at codon 986 of the CNGB1 protein (p.Asn986Ile). The asparagine residue is moderately conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant is present in population databases (rs201162411, ExAC 0.5%). This variant has been observed individuals affected with retinitis pigmentosa (PMID: 28041643, 28056120, 29912909, 28559085) and segregated with retinitis pigmentosa in several families (PMID: 28056120, 21147909). In at least one individual, this variant appears to be in trans (on the opposite chromosome) from a pathogenic variant, consistent with autosomal recessive inheritance. ClinVar contains an entry for this variant (Variation ID: 166891). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073599 SCV001239150 pathogenic Retinal dystrophy 2019-07-09 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000153040 SCV001245983 pathogenic not provided 2020-03-01 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504912 SCV000598713 likely pathogenic Retinitis pigmentosa 2015-01-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000504912 SCV000926547 likely pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Sharon lab,Hadassah-Hebrew University Medical Center RCV000504912 SCV001161021 likely pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research

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