Interpreting TP53 pathogenic variants: diagnostic complexities of mosaic and germline variants.

Diagnostic complexities of distinguishing mosaic from germline *TP53* pathogenic variants

This Journal of Medical Genetics case report illustrates diagnostic pitfalls of TP53 pathogenic variants through two observations. Case 1 describes a somatic mosaic TP53 variant (VAF 19% in blood) initially missed by panel sequencing in a 24-year-old with early breast cancer. Case 2 presents two identical TP53 variants in two different tissues, initially suggesting somatic mosaicism but ultimately attributable to a germline variant.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

These two cases highlight that interpreting TP53 variants in a mosaicism context is particularly challenging, with major surveillance implications depending on the conclusion. Combined with article #1 on hypomorphic variants, this makes for an exceptionally rich week on TP53 in oncogenetics practice.

Clinical impact: 2/3 · Evidence strength: 2/3 · Novelty: 1/2 · Sample size: 0/1 · Publication status: 1/1 → Total: 6/10