Rapid resolution of variants of uncertain significance (VUS). A complementary role for zebrafish in the era of multi-million-dollar therapies.

Genomic screening increasingly reveals variants of uncertain significance, forcing clinicians to make high-stakes decisions as million-dollar drug and gene-replacement therapies emerge. Rapid in vivo zebrafish assays can help to resolve variant pathogenicity within weeks, providing organism-level evidence that informs treatment decisions, prevents unnecessary interventions, and strengthens precision medicine.