Genetic tests currently used in routine diagnostics are designed to detect almost all types of genetic aberrations that may cause disease. However, in some cases, aberrations can be detected, but remain partly unresolved: e.g., the detection of a large duplication often does not entail information on its point of insertion in the genome, which could be crucial to determine its pathogenicity. This study describes an effective diagnostic pipeline aimed at solving these and similar cases, leveraging optical genome mapping (OGM). It describes OGM as a follow-up method for characterizing aberrations difficult to resolve otherwise, adding clinically relevant information. (By Dr. Paul Dremsek, https://jmg.bmj.com/content/early/2024/12/09/jmg-2024-110265 )