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

TP53

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.

Analysis by Dr Thibaut Benquey