ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.844C>G (p.Arg282Gly) (rs28934574)

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Total submissions: 22
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129010 SCV000172907 pathogenic Hereditary cancer-predisposing syndrome 2019-03-01 criteria provided, single submitter clinical testing The p.R282G pathogenic mutation (also known as c.844C>G), located in coding exon 7 of the TP53 gene, results from a C to G substitution at nucleotide position 844. The arginine at codon 282 is replaced by glycine, an amino acid with dissimilar properties. This mutation is in the DNA binding domain of the p53 protein and is reported to have loss of transactivation capacity and predicted to affect several p53 isoforms (IARC TP53 database; Kato S et al. Proc. Natl. Acad. Sci. USA. 2003 Jul;100:8424-9). Studies conducted in human cell lines indicate this alteration is deficient at growth suppression (Kotler E et al. Mol.Cell, 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet., 2018 Oct;50:1381-1387). It was previously identified in a patient with primary orbital liposarcoma whose family met diagnostic criteria for Li-Fraumeni syndrome (LFS) (Poli T et al. Tumori; 91:96-100). Additionally, two other missense mutations occurring at the same codon have been reported (p.R282Q and p.R282W). In one study, the p.R282Q mutation was reported in a 14-year-old male with a soft tissue sarcoma who was later diagnosed with an osteosarcoma and lung cancer (Chompret et al. 2000 British J Cancer 82(12):1932-1937). The p.R282W mutation was detected in a patient with contralateral breast cancer at age 32 (Heyman et al. 2010 Radiation Oncology 5:104), and in a kindred with clinical LFS, however, specific clinical information was not provided (Wu et al. 2011 Hum Genet 129:663-673). Based on the supporting evidence, the p.R282G alteration is interpreted as a disease-causing mutation.
Invitae RCV001380073 SCV001578015 pathogenic Li-Fraumeni syndrome 2020-08-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 282 of the TP53 protein (p.Arg282Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Li-Fraumeni Syndrome (PMID: 15850016, 28802053, 26014290, 26556299). ClinVar contains an entry for this variant (Variation ID: 140821). Experimental studies have shown that this variant affects TP53 protein function (PMID: 12826609, 29979965, 30224644, 21343334, 23246812). This variant disrupts the p.Arg282 amino acid residue in TP53. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25584008, 21305319, 21761402, 1565143, 11370630, 1565144, 22672556, 19468865, 17606709, 12826609). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Database of Curated Mutations (DoCM) RCV000440446 SCV000509593 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422747 SCV000509594 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430393 SCV000509595 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440653 SCV000509596 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422134 SCV000509597 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432433 SCV000509598 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442627 SCV000509599 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422367 SCV000509600 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431764 SCV000509601 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442540 SCV000509602 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425179 SCV000509603 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435503 SCV000509604 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445294 SCV000509605 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427647 SCV000509606 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437895 SCV000509607 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419333 SCV000509608 likely pathogenic Non-Hodgkin lymphoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430047 SCV000509609 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437219 SCV000509610 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419993 SCV000509611 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785299 SCV000923867 likely pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research

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