Total submissions: 23
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000115726 | SCV000149635 | pathogenic | not provided | 2014-02-06 | criteria provided, single submitter | clinical testing | This variant is denoted TP53 c.535C>T at the cDNA level, p.His179Tyr (H179Y) at the protein level, and results in the change of a Histidine to a Tyrosine (CAT>TAT) in exon 5. This mutation has been observed as a somatic mutation in over 100 different cancers but has only been observed as a germline mutation in one patient with a history of six cancers, most being classic Li-Fraumeni tumors: fibrosarcoma, adrenal cortical carcinoma, osteosarcoma, ductal carcinoma in situ, infiltrating ductal carcinoma and adenocarcinoma of the pancreas (IARC TP53 Database, Lefrou 2006). Two in vitro functional assays have shown that this mutation has similar protein activity as cells null for the p53 protein (Ko 2002, Yang 2007). TP53 His179Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Variant Server, indicating it is not a common benign variant in these populations. This mutation is a non-conservative substitution in which a positive polar amino acid is replaced with a neutral polar one, altering a position that is well conserved throughout evolution and is located in within the DNA-binding domain and the region that interacts with HIPK1, ZNF385A, FBX042 and AXIN1. Based on the currently available information, we consider TP53 His179Tyr to be a pathogenic mutation This variant has been seen apparently mosaic. The variant is found in BR-OV-HEREDIC panel(s). |
Invitae | RCV000555493 | SCV000629834 | pathogenic | Li-Fraumeni syndrome | 2019-04-01 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 179 of the TP53 protein (p.His179Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with a personal and/or family history of Li-Fraumeni syndrome, including one individual in whom it was reported to arise de novo (PMID: 16633321, 18511570, 25433984). ClinVar contains an entry for this variant (Variation ID: 127815). Experimental studies in cell lines and yeast have shown that this missense change disrupts TP53 protein function and acts in a dominant-negative manner (PMID: 12509279, 17530187, 12826609, 26497680, 12726864, 11896595). For these reasons, this variant has been classified as Pathogenic. |
Counsyl | RCV000663095 | SCV000786200 | likely pathogenic | Li-Fraumeni syndrome 1 | 2018-03-16 | criteria provided, single submitter | clinical testing | |
Database of Curated Mutations |
RCV000424007 | SCV000508352 | likely pathogenic | Small cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434725 | SCV000508353 | likely pathogenic | Malignant melanoma of skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444364 | SCV000508354 | likely pathogenic | Breast neoplasm | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000427283 | SCV000508355 | likely pathogenic | Neoplasm of brain | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000435360 | SCV000508356 | likely pathogenic | Malignant neoplasm of body of uterus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000444227 | SCV000508357 | likely pathogenic | Lung adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000424716 | SCV000508358 | likely pathogenic | Squamous cell carcinoma of the head and neck | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436304 | SCV000508359 | likely pathogenic | Uterine Carcinosarcoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419024 | SCV000508360 | likely pathogenic | Squamous cell carcinoma of the skin | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000428854 | SCV000508361 | likely pathogenic | Acute myeloid leukemia | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000436095 | SCV000508362 | likely pathogenic | Carcinoma of gallbladder | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000419735 | SCV000508363 | likely pathogenic | Glioblastoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000430411 | SCV000508364 | likely pathogenic | Pancreatic adenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000440222 | SCV000508365 | likely pathogenic | Carcinoma of esophagus | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423020 | SCV000508366 | likely pathogenic | Squamous cell lung carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000431087 | SCV000508367 | likely pathogenic | Ovarian Serous Cystadenocarcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000441827 | SCV000508368 | likely pathogenic | Hepatocellular carcinoma | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000423688 | SCV000508369 | likely pathogenic | Adenocarcinoma of stomach | 2016-05-31 | no assertion criteria provided | literature only | |
Database of Curated Mutations |
RCV000434379 | SCV000508370 | likely pathogenic | Neoplasm of the large intestine | 2016-05-31 | no assertion criteria provided | literature only | |
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne, |
RCV000785312 | SCV000923880 | likely pathogenic | Neoplasm of ovary | 2018-12-01 | no assertion criteria provided | research |