ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.607G>T (p.Gly203Trp) (rs1012377281)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531975 SCV000629337 uncertain significance Retinoblastoma 2017-03-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with tryptophan at codon 203 of the RB1 protein (p.Gly203Trp). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and tryptophan. This variant also falls at the last nucleotide of exon 6 of the RB1 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RB1-related disease. 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 variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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