ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.325T>G (p.Phe109Val) (rs1057523496)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434126 SCV000532251 likely pathogenic not provided 2016-11-23 criteria provided, single submitter clinical testing The F109V variant in the TP53 gene has been previously reported as a somatic variant in multiple different types of neoplasms, but has not been reported in the germline (for examples, see Aissi et al., 2014; Lee et al., 2013; Tanase et al., 2015). This variant is reported as having nonfunctional transactivation in the International Agency for Research on Cancer (IARC) TP53 database based on functional assays by Kato et al. (2003). The F109V variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The F109V variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Phenylalanine are tolerated across species. Missense variants in nearby residues (G105C, S106R, R110H, R110P, R110L) have been reported in the Human Gene Mutation Database in association with TP53-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Based on the currently available information, F109V is a strong candidate for a pathogenic variant. However, the possibility it is a rare benign variant cannot be excluded.

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.