ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.940-1G>A (rs1131690860)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492095 SCV000580790 pathogenic Hereditary cancer-predisposing syndrome 2013-04-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity,Other acmg-defined mutation (i.e. initiation codon or gross deletion)
Invitae RCV000701287 SCV000830080 pathogenic Retinoblastoma 2018-01-27 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 9 of the RB1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with bilateral retinoblastoma (PMID: 27582626). ClinVar contains an entry for this variant (Variation ID: 428678). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and 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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