ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.221C>G (p.Ala74Gly)

dbSNP: rs764472420
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000550936 SCV000629301 uncertain significance Retinoblastoma 2017-02-15 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This variant is present in population databases (rs764472420, ExAC 0.009%) but has not been reported in the literature in individuals with an RB1-related disease. This sequence change replaces alanine with glycine at codon 74 of the RB1 protein (p.Ala74Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies.

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