ClinVar Miner

Submissions for variant NM_000321.2(RB1):c.2518G>A (p.Gly840Arg) (rs374157786)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232184 SCV000284622 uncertain significance Retinoblastoma 2018-03-14 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 840 of the RB1 protein (p.Gly840Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs374157786, ExAC 0.002%) but has not been reported in the literature in individuals with an RB1-related disease. ClinVar contains an entry for this variant (Variation ID: 237670). 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. 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. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000232184 SCV000838928 uncertain significance Retinoblastoma 2018-07-02 criteria provided, single submitter clinical testing

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