ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.587G>C (p.Arg196Pro) (rs483352697)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216410 SCV000274927 likely pathogenic Hereditary cancer-predisposing syndrome 2019-04-17 criteria provided, single submitter clinical testing The p.R196P variant (also known as c.587G>C), located in coding exon 5 of the TP53 gene, results from a G to C substitution at nucleotide position 587. The arginine at codon 196 is replaced by proline, an amino acid with dissimilar properties. This alteration has been reported as a germline mutation in two individuals with Li-Fraumeni syndrome, including a male with a brain tumor at age 1 and osteosarcoma at age 16 (Rines RD et al. Carcinogenesis 1998 Jun;19(6):979-84; Petitjean A et al. IARC TP53 database [version R17, November 2013]. Hum Mutat. 2007 Jun;28(6):622-9). This alteration was also reported in a proband with breast cancer at age 28 whose mother had breast cancer at age 29 (Bonache S et al. J. Cancer Res. Clin. Oncol. 2018 Dec;144(12):2495-2513). This variant is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation capacity and a dominant negative effect in yeast based assays (Kato S et al. Proc Natl Acad Sci USA. 2003 Jul 8;100(14):8424-9; Monti P, Mol. Cancer Res. 2011 Mar; 9(3):271-9). 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). 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, this variant is likely to be pathogenic.
Color Health, Inc RCV000216410 SCV001345629 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-21 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000433800 SCV000509180 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440531 SCV000509181 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423798 SCV000509182 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434064 SCV000509183 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443813 SCV000509184 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427483 SCV000509185 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431695 SCV000509186 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443927 SCV000509187 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425092 SCV000509188 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435372 SCV000509189 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418400 SCV000509190 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426017 SCV000509191 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436292 SCV000509192 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419494 SCV000509193 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429772 SCV000509194 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440866 SCV000509195 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only

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