ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.2557T>C (p.Cys853Arg)

gnomAD frequency: 0.00001  dbSNP: rs1295589257
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000693294 SCV000821156 uncertain significance Retinoblastoma 2023-04-11 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 853 of the RB1 protein (p.Cys853Arg). This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RB1 protein function. ClinVar contains an entry for this variant (Variation ID: 572008). This variant has not been reported in the literature in individuals affected with RB1-related conditions.
Ambry Genetics RCV003163168 SCV003871067 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-08 criteria provided, single submitter clinical testing The p.C853R variant (also known as c.2557T>C), located in coding exon 25 of the RB1 gene, results from a T to C substitution at nucleotide position 2557. The cysteine at codon 853 is replaced by arginine, an amino acid with highly dissimilar properties. This alteration was detected in 1/224 unrelated Brazilian individuals with breast cancer (Sandoval RL et al. PLoS One, 2021 Feb;16:e0247363). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.