ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.659A>C (p.Tyr220Ser) (rs121912666)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 22
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Database of Curated Mutations (DoCM) RCV000443214 SCV000510209 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425801 SCV000510210 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436486 SCV000510211 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418406 SCV000510212 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429097 SCV000510213 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435597 SCV000510214 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417473 SCV000510215 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428157 SCV000510216 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441465 SCV000510217 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424238 SCV000510218 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430581 SCV000510219 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441285 SCV000510220 likely pathogenic Papillary renal cell carcinoma, sporadic 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423167 SCV000510221 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433786 SCV000510222 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445060 SCV000510223 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422874 SCV000510224 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432708 SCV000510225 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000444276 SCV000510226 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425300 SCV000510227 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000785481 SCV000924053 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research
Invitae RCV000472593 SCV000545350 pathogenic Li-Fraumeni syndrome 2018-11-16 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with serine at codon 220 of the TP53 protein (p.Tyr220Ser). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals and families affected with Li-Fraumeni syndrome (LFS) or Li-Fraumeni-associated cancers, and has been shown to segregate with disease in one family (PMID: 15977174, 17606709, 20234365, 19556618). ClinVar contains an entry for this variant (Variation ID: 12383). Experimental studies have shown that this variant disrupts transcriptional activity in yeast-based assays and confers angiogenic properties in cell cultures (PMID: 12826609, 15977174, 21343334). A different missense substitution at this codon (p.Tyr220Cys) has been determined to be pathogenic (PMID:  19101993, 20028212,20407015, 18307025,, 24603336 ). This suggests that the tyrosine residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000013183 SCV000033430 pathogenic Li-Fraumeni syndrome 1 2005-08-01 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.