ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.1735C>T (p.Arg579Ter) (rs121913305)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000114677 SCV000551816 pathogenic Retinoblastoma 2018-08-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg579*) 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 as a recurrent variant in individuals affected with retinoblastoma (PMID: 12541220, 25754945, 27582626, 7704558, 27021801). ClinVar contains an entry for this variant (Variation ID: 126785). Loss-of-function variants in RB1 are known to be pathogenic (PMID: 17096365). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000492238 SCV000580782 pathogenic Hereditary cancer-predisposing syndrome 2017-02-17 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)
GeneDx RCV000521112 SCV000617263 pathogenic not provided 2017-10-05 criteria provided, single submitter clinical testing This variant is denoted RB1 c.1735C>T at the cDNA level and p.Arg579Ter (R579X) at the protein level.The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and ispredicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay.This variant has been reported as a recurrent variant in individuals with bilateral and unilateral retinoblastoma(Blanquet 1995, Richter 2003, Alonso 2005, Abouzeid 2007, Pradhan 2010, Saliminejad 2013, Mohd Khalid, 2015, Sagi2015, Singh 2016, Yousef 2017). We consider this variant to be pathogenic
Genetic Diagnostic Laboratory,University of Pennsylvania School of Medicine RCV000114677 SCV000087375 pathogenic Retinoblastoma 2013-09-16 no assertion criteria provided clinical testing
Database of Curated Mutations (DoCM) RCV000114677 SCV000505677 likely pathogenic Retinoblastoma 2015-07-14 no assertion criteria provided literature only

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