ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.451C>A (p.Pro151Thr) (rs28934874)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 21
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130617 SCV000185493 likely pathogenic Hereditary cancer-predisposing syndrome 2016-03-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Good segregation with disease (lod 1.5-3 = 5-9 meioses),Deficient protein function in appropriate functional assay(s),Well-characterized mutation at same position,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Database of Curated Mutations (DoCM) RCV000437544 SCV000508983 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418145 SCV000508984 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428384 SCV000508985 likely pathogenic Adenoid cystic carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435159 SCV000508986 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417493 SCV000508987 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429500 SCV000508988 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439740 SCV000508989 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422094 SCV000508990 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428836 SCV000508991 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440812 SCV000508992 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423161 SCV000508993 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000433405 SCV000508994 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443817 SCV000508995 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424222 SCV000508996 likely pathogenic Carcinoma of esophagus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434485 SCV000508997 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000442802 SCV000508998 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425139 SCV000508999 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
GeneDx RCV000520731 SCV000617735 likely pathogenic not provided 2018-08-24 criteria provided, single submitter clinical testing This variant is denoted TP53 c.451C>A at the cDNA level, p.Pro151Thr (P151T) at the protein level, and results in the change of a Proline to a Threonine (CCC>ACC). This variant has been observed in two individuals with early-onset breast cancer, one of whom had a family history of sarcoma and adrenocortical carcinoma (Vahteristo 2001, Maxwell 2015). Although this variant is reported as having non-functional transactivation in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003), and Monti et al. (2011) also found a significant reduction in transactivation activity, this variant was not found to cause a dominant-negative effect and only had a slight impact on growth suppression (Monti 2011, Kotler 2018). TP53 Pro151Thr was not observed in large population cohorts (Lek 2016). This variant is located in the DNA binding domain (Bode 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on the currently available evidence, we consider TP53 Pro151Thr to be a likely pathogenic variant.
Invitae RCV000691152 SCV000818896 likely pathogenic Li-Fraumeni syndrome 2018-05-04 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 151 of the TP53 protein (p.Pro151Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with early-onset breast cancer and family histories of TP53-related disease (PMID: 11479205, 25503501). This variant was reported to segregate with TP53-related disease in one of these families, though pedigree data was not provided (PMID: 11479205). ClinVar contains an entry for this variant (Variation ID: 12369). Experimental studies in yeast have shown that this variant impairs the transcriptional transactivation activity of the TP53 protein (PMID: 12826609, 21343334). A different missense substitution at this codon (p.Pro151Ser) has been determined to be pathogenic (PMID: 7881428, 20522432, 20128691, 12826609, 21343334, 16861262, 10713666, 23625637). This suggests that the proline residue is critical for TP53 protein function and that other missense substitutions at this position may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000013168 SCV000033415 pathogenic Breast adenocarcinoma 1993-07-01 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.