Total submissions: 24
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000220461 | SCV000274991 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-04-21 | criteria provided, single submitter | clinical testing | The p.R213P pathogenic mutation (also known as c.638G>C), located in coding exon 5 of the TP53 gene, results from a G to C substitution at nucleotide position 638. The arginine at codon 213 is replaced by proline, an amino acid with dissimilar properties. This alteration was first described segregating with disease in a family satisfying clinical criteria for classic Li-Fraumeni syndrome (LFS), (Dockhorn-Dworniczak B et al, <span style="font-family:arial,sans-serif">Eur. J. Cancer 1996 Jul; 32A(8):1359-65). Tumor analyses from p.R213P-carriers in this family revealed increased nuclear p53 staining as well as somatic loss-of-heterozygosity (LOH). This variant is located in the DNA binding domain of TP53 and is reported to have loss of transactivation capacity, and a moderate dominant negative effect in yeast based functional studies (IARC TP53 database; Kato S et al. Proc<span style="font-family:arial,sans-serif"> Natl<span style="font-family:arial,sans-serif"> Acad<span style="font-family:arial,sans-serif"> Sci USA. 2003 Jul 8;100(14):8424-9; Monti P et al. <span style="font-family:arial,sans-serif">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). Based on internal structural analysis, this variant is anticipated to result in a significant decrease in structural stability (Cho Y et al., <span style="font-family:arial,sans-serif">Science 1994 Jul; 265(5170):346-55). In addition, another alteration at the same codon, p.R213Q, has been identified in multiple suspected-LFS patients and is considered pathogenic (Becherini et al. Neuropathol<span style="font-family:arial,sans-serif"> Appl<span style="font-family:arial,sans-serif"> Neurobiol. 2008 Oct;34(5):564-8; Ruijs MW et al. <span style="font-family:arial,sans-serif">J Med Genet. 2010 Jun;47(6):421-8; Achatz MI et al. <span style="font-family:arial,sans-serif">Cancer Lett<span style="font-family:arial,sans-serif">. 2007 Jan 8;245(1-2):96-102). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
ARUP Laboratories, |
RCV000506128 | SCV000605421 | likely pathogenic | not specified | 2016-11-02 | criteria provided, single submitter | clinical testing | |
Database of Curated Mutations |
RCV000429975 | SCV000509240 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440212 | SCV000509241 | likely pathogenic | Nasopharyngeal Neoplasms | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423147 | SCV000509242 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000433848 | SCV000509243 | likely pathogenic | Adrenocortical carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000441029 | SCV000509244 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423776 | SCV000509245 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434458 | SCV000509246 | likely pathogenic | Transitional cell carcinoma of the bladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443850 | SCV000509247 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424407 | SCV000509248 | likely pathogenic | Ovarian Serous Cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431639 | SCV000509249 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000443926 | SCV000509250 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000425014 | SCV000509251 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435742 | SCV000509252 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000418520 | SCV000509253 | likely pathogenic | Adenocarcinoma of prostate | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000426111 | SCV000509254 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436779 | SCV000509255 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419521 | SCV000509256 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430230 | SCV000509257 | likely pathogenic | Adenoid cystic carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440917 | SCV000509258 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000420213 | SCV000509259 | likely pathogenic | Squamous cell carcinoma of the skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430895 | SCV000509260 | likely pathogenic | Renal cell carcinoma, papillary, 1 | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000441598 | SCV000509261 | likely pathogenic | Uterine Carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only |