ClinVar Miner

Submissions for variant NM_000546.6(TP53):c.725G>T (p.Cys242Phe)

dbSNP: rs121912655
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688366 SCV000815974 uncertain significance Li-Fraumeni syndrome 2023-09-21 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change affects TP53 function (PMID: 12826609, 29979965). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 12826609, 29979965, 30224644) indicates that this missense variant is expected to disrupt TP53 function. ClinVar contains an entry for this variant (Variation ID: 376578). This missense change has been observed in individual(s) with breast or ovarian cancer (PMID: 29470806). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 242 of the TP53 protein (p.Cys242Phe).
Ambry Genetics RCV002379285 SCV002671484 pathogenic Hereditary cancer-predisposing syndrome 2023-09-13 criteria provided, single submitter clinical testing The p.C242F pathogenic mutation (also known as c.725G>T), located in coding exon 6 of the TP53 gene, results from a G to T substitution at nucleotide position 725. The cysteine at codon 242 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration has been identified in an Indian breast/ovarian cancer cohort (Singh J et al. Breast Cancer Res. Treat., 2018 Jul;170:189-196). This alteration has been reported as a germline alteration and as a somatic alteration in various tumors by the IARC TP53 database (Bouaoun L et al. IARC TP53 database [version 20, July 2019]. Hum. Mutat. 2016 Sep;37:865-76). This alteration is in the DNA binding domain of the TP53 protein and is reported to have loss of transactivation in yeast based assays (IARC TP53 database: Kato S et al. Proc. Natl. Acad. Sci. USA 2003 Jul;100:8424-9). Studies conducted in human cell lines are equivocal about this variant's ability to suppress cell growth (Kotler E et al. Mol. Cell 2018 Jul;71:178-190.e8; Giacomelli AO et al. Nat. Genet. 2018 Oct;50:1381-1387). This alteration is located in the functionally critical DNA binding domain, and it is one of four amino acid residues required for zinc binding and protein stabilization (Cho Y et al. Science, 1994 Jul;265:346-55). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Database of Curated Mutations (DoCM) RCV000433671 SCV000507769 likely pathogenic B-cell chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442449 SCV000507770 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427153 SCV000507771 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438269 SCV000507772 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442305 SCV000507773 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424746 SCV000507774 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435022 SCV000507775 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417879 SCV000507776 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425032 SCV000507777 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435743 SCV000507778 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418512 SCV000507779 likely pathogenic Uterine carcinosarcoma 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne RCV000785473 SCV000924045 likely pathogenic Neoplasm of ovary 2018-12-01 no assertion criteria provided research

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.