ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.724T>A (p.Cys242Ser) (rs1057519982)

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
Counsyl RCV000662594 SCV000785224 uncertain significance Li-Fraumeni syndrome 1 2017-06-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001026200 SCV001188535 likely pathogenic Hereditary cancer-predisposing syndrome 2019-04-01 criteria provided, single submitter clinical testing The p.C242S variant (also known as c.724T>A), located in coding exon 6 of the TP53 gene, results from a T to A substitution at nucleotide position 724. The cysteine at codon 242 is replaced by serine, an amino acid with dissimilar properties. 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 variant 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 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 majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV001325155 SCV001516134 uncertain significance Li-Fraumeni syndrome 2020-08-28 criteria provided, single submitter clinical testing This sequence change replaces cysteine with serine at codon 242 of the TP53 protein (p.Cys242Ser). The cysteine residue is highly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with ovarian cancer (PMID: 30918304). ClinVar contains an entry for this variant (Variation ID: 376579). Experimental studies have shown that this variant affects TP53 protein function (PMID: 12826609, 30224644, 29979965, 19681600, 20407015, 17170001, 10713666). This variant disrupts the p.Cys242 amino acid residue in TP53. Other variant(s) that disrupt this residue have been observed in individuals with TP53-related conditions (PMID: 1679237, 8164043, 9839505, 25896519, 21059199, 12826609), suggesting that it is a clinically significant residue. As a result, 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.
Database of Curated Mutations (DoCM) RCV000429187 SCV000507780 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439881 SCV000507781 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419559 SCV000507782 likely pathogenic Chronic lymphocytic leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430244 SCV000507783 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440943 SCV000507784 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423712 SCV000507785 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434352 SCV000507786 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441578 SCV000507787 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424356 SCV000507788 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431566 SCV000507789 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442629 SCV000507790 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only

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.