ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2134T>G (p.Cys712Gly)

dbSNP: rs137853296
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001361083 SCV001557046 uncertain significance Retinoblastoma 2022-03-07 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 712 of the RB1 protein (p.Cys712Gly). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 1052825). This variant has not been reported in the literature in individuals affected with RB1-related conditions. This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV004671368 SCV005160557 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-06 criteria provided, single submitter clinical testing The p.C712G variant (also known as c.2134T>G), located in coding exon 21 of the RB1 gene, results from a T to G substitution at nucleotide position 2134. The cysteine at codon 712 is replaced by glycine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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