Characteristics predicting reduced penetrance variants in the high-risk cancer predisposition gene TP53.

ABSTRACT: Disease-causing variants with penetrance that is lower than the average expected for a given gene complicate classification, even when using gene-specific guidelines. For TP53, a gene associated with some of the highest cancer risks, even reduced penetrance disease-predisposition variants remain clinically actionable. We conducted a review of ClinVar submissions to identify TP53 variants flagged as having reduced penetrance by genetic testing laboratories and analyzed functional, bioinformatic, immunogenicity, frequency, and clinical features of these variants compared with standard pathogenic and benign variants. Our findings show that reported reduced penetrance TP53 variants are more likely to exhibit intermediate functional activity in multiple assays and are predicted as deleterious w

SUBMITTER: Fortuno C 

PROVIDER: S-EPMC12337872 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature