ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.1814+3A>G (rs376886420)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000238879 SCV000296904 uncertain significance Retinoblastoma 2015-10-30 criteria provided, single submitter clinical testing
Invitae RCV000238879 SCV000551819 uncertain significance Retinoblastoma 2017-05-25 criteria provided, single submitter clinical testing This sequence change falls in intron 18 of the RB1 gene. It does not directly change the encoded amino acid sequence of the RB1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs376886420, ExAC 0.01%) but has not been reported in the literature in individuals with a RB1-related disease. ClinVar contains an entry for this variant (Variation ID: 252476). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.

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