ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.536A>T (p.His179Leu) (rs1057519991)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 20
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Database of Curated Mutations (DoCM) RCV000432746 SCV000508390 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439930 SCV000508391 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421837 SCV000508392 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432531 SCV000508393 likely pathogenic Squamous cell carcinoma of the skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444683 SCV000508394 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426806 SCV000508395 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433134 SCV000508396 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443637 SCV000508397 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427517 SCV000508398 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438217 SCV000508399 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420124 SCV000508400 likely pathogenic Carcinoma of gallbladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427330 SCV000508401 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435347 SCV000508402 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418129 SCV000508403 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427941 SCV000508404 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438631 SCV000508405 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418835 SCV000508406 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429543 SCV000508407 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439318 SCV000508408 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Invitae RCV000705316 SCV000834307 uncertain significance Li-Fraumeni syndrome 2018-06-28 criteria provided, single submitter clinical testing This sequence change replaces histidine with leucine at codon 179 of the TP53 protein (p.His179Leu). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 376608). Experimental studies have shown that this missense change impairs transcriptional transactivation activity of the TP53 protein, reduces apoptosis activity and confers cisplatin-sensitivity and increased cell mobility to cells carrying this variant, and acts in a dominant-negative fashion to inhibit function of wild-type protein (PMID: 12826609, 16861262, 22114072, 23713777). In addition, cells carrying this variant transplanted in mice induce tumor formation more rapidly than cells carrying wild-type TP53 (PMID: 9049183). Variants that disrupt the 179 amino acid residue in TP53 have been observed in affected individuals (PMID: 19556618, 16633321, 18511570, 25433984). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.