ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.580C>T (p.Leu194Phe) (rs587780071)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Database of Curated Mutations (DoCM) RCV000419908 SCV000508858 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426684 SCV000508859 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436065 SCV000508860 likely pathogenic Transitional cell carcinoma of the bladder 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418414 SCV000508861 likely pathogenic Ovarian Serous Cystadenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429595 SCV000508862 likely pathogenic Neoplasm of brain 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439843 SCV000508863 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417813 SCV000508864 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428029 SCV000508865 likely pathogenic Lung adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439186 SCV000508866 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421548 SCV000508867 likely pathogenic Uterine cervical neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434383 SCV000508868 likely pathogenic Hepatocellular carcinoma 2016-05-31 no assertion criteria provided literature only
GeneDx RCV000115728 SCV000149637 likely pathogenic not provided 2017-11-12 criteria provided, single submitter clinical testing This variant is denoted TP53 c.580C>T at the cDNA level, p.Leu194Phe (L194F) at the protein level, and results in the change of a Leucine to a Phenylalanine (CTT>TTT). This variant has been observed in an individual with bilateral breast cancer and in an individual with lung cancer in association with Li-Fraumeni syndrome (Melhem-Bertrandt 2012, Villani 2016). This variant is reported as having non-functional transactivation (TA) in the International Agency for Research on Cancer TP53 database based on functional assays by Kato et al. (2003) and was reported to have absent TA activity in two other independent studies (Epstein 1998, Brazda 2006). Tumor derived cell lines harboring Leu194Phe lose the ability to form complexes with BclXL/2 along with the ability to promote cytochrome c release, which are critical activities related to apoptosis (Mihara 2003, Tomita 2006). TP53 Leu194Phe was not observed in large population cohorts (Lek 2016). Since Leucine and Phenylalanine share similar properties, this is considered a conservative amino acid substitution. TP53 Leu194Phe is located in DNA binding domain (Bode 2004). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Based on the currently available evidence, we consider TP53 Leu194Phe to be a likely pathogenic variant.

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.