ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.1363C>T (p.Arg455Ter) (rs121913302)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492246 SCV000580762 pathogenic Hereditary cancer-predisposing syndrome 2018-04-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Database of Curated Mutations (DoCM) RCV000114729 SCV000505675 likely pathogenic Retinoblastoma 2015-07-14 no assertion criteria provided literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000486601 SCV000703952 pathogenic not provided 2016-11-22 criteria provided, single submitter clinical testing
GeneDx RCV000486601 SCV000568220 pathogenic not provided 2018-02-26 criteria provided, single submitter clinical testing This variant is denoted RB1 c.1363C>T at the cDNA level and p.Arg455Ter (R455X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in many individuals with isolated bilateral and/or familial retinoblastoma of various ethnic backgrounds (Lohmann 1996, Richter 2003, Houdayer 2004, Taylor 2007, Chen 2010, Abidi 2011, Barbosa 2013, Ayari-Jeridi 2014, Amitrano 2015, Tomar 2017). We consider RB1 Arg455Ter to be pathogenic.
Genetic Diagnostic Laboratory,University of Pennsylvania School of Medicine RCV000114729 SCV000087397 pathogenic Retinoblastoma 2013-09-16 no assertion criteria provided research
Invitae RCV000114729 SCV000629277 pathogenic Retinoblastoma 2018-08-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg455*) in the RB1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in several individuals affected with retinoblastoma (PMID: 8651278, 20059380, 27582626, 24791139, 23532519), including an affected individual in whom the variant had arisen de novo (PMID: 25928201). ClinVar contains an entry for this variant (Variation ID: 126837). Loss-of-function variants in RB1 are known to be pathogenic (PMID: 17096365). For these reasons, this variant has been classified as Pathogenic.

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