ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2134T>A (p.Cys712Ser)

dbSNP: rs137853296
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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 RCV002021313 SCV002311102 uncertain significance Retinoblastoma 2021-04-11 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Cys712 amino acid residue in RB1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9671401, 10671068, 11668642, 22084214). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RB1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 712 of the RB1 protein (p.Cys712Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine.

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