ClinVar Miner

Submissions for variant NM_000321.3(RB1):c.1654C>T (p.Arg552Ter)

dbSNP: rs121913303
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Diagnostic Laboratory, University of Pennsylvania School of Medicine RCV000114733 SCV000087356 pathogenic Retinoblastoma 2024-05-20 criteria provided, single submitter clinical testing Case and Pedigree Information: BILATERAL CASES:6, UNILATERAL CASES:4, TOTAL CASES:10, PEDIGREES:10. ACMG Codes Applied:PVS1, PM2, PS4M
Invitae RCV000114733 SCV000551833 pathogenic Retinoblastoma 2022-12-11 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg552*) in the RB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RB1 are known to be pathogenic (PMID: 17096365). This premature translational stop signal has been observed in individual(s) with retinoblastoma (PMID: 7704558, 22219649, 24791139, 25754945, 27582626). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 126840).
Ambry Genetics RCV000492730 SCV000580767 pathogenic Hereditary cancer-predisposing syndrome 2017-09-15 criteria provided, single submitter clinical testing The p.R552* pathogenic mutation (also known as c.1654C>T), located in coding exon 17 of the RB1 gene, results from a C to T substitution at nucleotide position 1654. This changes the amino acid from an arginine to a stop codon within coding exon 17. This alteration, often designated as "R552X" in published literature, has been detected in the germline of multiple patients diagnosed with bilateral retinoblastoma, and has been confirmed as a somatic mutation in RB tumor DNA in other patients (Braggio E et al. J Clin Pathol. 2004 Jun;57(6):585-90; Richter S et al. Am J Hum Genet. 2003 Feb;72(2):253-69; He MY et al. Mol Vis. 2014 Apr 25;20:545-52). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Department of Pediatrics, Memorial Sloan Kettering Cancer Center RCV000114733 SCV001478164 pathogenic Retinoblastoma 2020-12-15 criteria provided, single submitter research
Database of Curated Mutations (DoCM) RCV000114733 SCV000504839 likely pathogenic Retinoblastoma 2015-07-14 no assertion criteria provided literature only
Laboratory of Urology, Hospital Clinic de Barcelona RCV003332118 SCV004040510 pathogenic Malignant tumor of urinary bladder no assertion criteria provided research

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.