Total submissions: 18
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 | RCV000216410 | SCV001345629 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-21 | criteria provided, single submitter | clinical testing | |
Database of Curated Mutations |
RCV000433800 | SCV000509180 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440531 | SCV000509181 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
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 |
RCV000434064 | SCV000509183 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443813 | SCV000509184 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427483 | SCV000509185 | likely pathogenic | Renal cell carcinoma, papillary, 1 | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431695 | SCV000509186 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443927 | SCV000509187 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425092 | SCV000509188 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435372 | SCV000509189 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418400 | SCV000509190 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426017 | SCV000509191 | likely pathogenic | Squamous cell carcinoma of the skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436292 | SCV000509192 | likely pathogenic | Multiple myeloma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419494 | SCV000509193 | likely pathogenic | Small cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000429772 | SCV000509194 | likely pathogenic | Ovarian Serous Cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440866 | SCV000509195 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only |