Performance of LFSPRO prediction in TP53 mutation status for prospectively collected probands.

LFSPRO probabilistic model based on family history — individual probability estimation of pathogenic TP53 variant

LFSPRO, a Mendelian probabilistic model using family history to estimate individual TP53 pathogenic variant probability, was evaluated prospectively in 178 probands undergoing clinical genetic counseling and germline TP53 testing. LFSPRO showed substantially superior discrimination over Chompret criteria: sensitivity 81% vs. 33%, specificity 88% vs. 65%, PPV 0.53 vs. 0.14, NPV 0.96 vs. 0.85, and AUC 0.88. The model is well-calibrated (observed/expected ratio 1.07), supporting its use in clinical decision-making for TP53 testing.

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

LFSPRO provides exactly what clinical geneticists need: a quantitative, well-calibrated probability rather than a binary criteria-met/not-met decision. An NPV of 0.96 allows more robust reassurance for patients not meeting classic criteria, while identifying TP53 carriers that Chompret would have missed (sensitivity 81% vs. 33%). This model should become the standard triage tool for germline TP53 testing.

Clinical impact : 3/3 · Evidence strength : 2/3 · Novelty : 2/2 · Sample size : 1/1 · Journal quality : 1/1 → Total : 9/10