Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Diagnostic Laboratory, |
RCV000013946 | SCV000087353 | pathogenic | Retinoblastoma | 2024-05-20 | criteria provided, single submitter | clinical testing | Case and Pedigree Information: BILATERAL CASES:9, UNILATERAL CASES:5, TOTAL CASES:14, PEDIGREES:14. ACMG Codes Applied:PVS1, PM2, PS4M |
| Ambry Genetics | RCV000492544 | SCV000580852 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-09-25 | criteria provided, single submitter | clinical testing | The p.R445* pathogenic mutation (also known as c.1333C>T), located in coding exon 14 of the RB1 gene, results from a C to T substitution at nucleotide position 1333. This changes the amino acid from an arginine to a stop codon within coding exon 14. This mutation has been detected in multiple individuals with retinoblastoma (Yandell DW et al. N. Engl. J. Med., 1989 Dec;321:1689-95; Richter S et al. Am J Hum Genet, 2003 Feb;72:253-69; Abouzeid H et al. Mol. Vis., 2007 Sep;13:1740-5; Dommering CJ et al. Fam Cancer, 2012 Jun;11:225-33; Seo SH et al. Clin Genet, 2013 May;83:494-6; He MY et al. Mol Vis, 2014 Apr;20:545-52; Dommering CJ et al. J Med Genet, 2014 Jun;51:366-74; Niederst MJ et al. Nat Commun, 2015 Mar;6:6377; Sagi M et al. Fam Cancer, 2015 Sep;14:471-80; Zhang J et al. N Engl J Med, 2015 Dec;373:2336-2346; Meric-Bernstam F et al. Ann Oncol, 2016 05;27:795-800; Singh J et al. Mol Vis, 2016 Aug;22:1036-47; Shahraki K et al. Eye (Lond), 2017 Apr;31:620-627; Tomar S et al. PLoS ONE, 2017 Jun;12:e0178776; Parma D et al. PLoS ONE, 2017 Dec;12:e0189736; Chaussade A et al. Eur J Med Genet, 2019 Mar;62:217-223; Lan X et al. Front Genet, 2020 Mar;11:142; Gupta H et al. BMC Med Genomics, 2021 Jul;14:188). Of note, this alteration is also designated as 1462C>T in published literature. 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. |
| Labcorp Genetics |
RCV000013946 | SCV000629276 | pathogenic | Retinoblastoma | 2025-01-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg445*) 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 variant is present in population databases (rs3092891, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with retinoblastoma (PMID: 2594029, 20447117, 22328814, 22963398, 26787237). ClinVar contains an entry for this variant (Variation ID: 13071). For these reasons, this variant has been classified as Pathogenic. |
| St. |
RCV000013946 | SCV000853191 | pathogenic | Retinoblastoma | 2016-06-17 | criteria provided, single submitter | clinical testing | This is a nonsense alteration in which a C is replaced by a T at coding position 1333 and is predicted to change an Arginine at codon 445 to a premature stop codon. |
| Fulgent Genetics, |
RCV002496351 | SCV002810564 | pathogenic | Bone osteosarcoma; Malignant tumor of urinary bladder; Small cell lung carcinoma; Retinoblastoma | 2021-12-22 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002508188 | SCV002817730 | pathogenic | not provided | 2022-06-29 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 29261756, 34190019, 22328814, 26787237, 34294096, 2594029) |
| OMIM | RCV000013946 | SCV000034193 | pathogenic | Retinoblastoma | 1989-12-21 | no assertion criteria provided | literature only |