The biology of hypomorphic TP53 variants and implications for clinical management.

Hypomorphic *TP53* variants with partial loss of function and distinct phenotype from classic LFS

This Clinical Cancer Research review details the biology of hypomorphic TP53 variants, an emerging class with partial loss of function and a phenotype distinct from classic Li-Fraumeni syndrome. Increased genetic testing identifies these variants more frequently, but their clinical management — surveillance, screening criteria, genetic counseling — differs from canonical LFS. The authors propose a biological and clinical framework for tailored management.

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Distinguishing hypomorphic TP53 variants from classic LFS is increasingly important in oncogenetics consultations. Applying full LFS surveillance protocols would be excessive; ignoring them insufficient. This review is timely guidance as genetic panels generate growing numbers of difficult-to-classify TP53 variants.

Clinical impact: 3/3 · Evidence strength: 3/3 · Novelty: 2/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 10/10