Abstract

In clinical practice, sequencing of the whole exome (1–2% of the genome) in patients with a suspected genetic disorder has rapidly
expanded due to its high diagnostic yield (~30%). The exome dataset (>80,000 genetic variants) may also contain secondary findings – pathogenic variants not responsible for the patient’s primary health concern. Secondary findings linked to medically
actionable monogenic diseases affect about 1–3% of the general population. The onset of symptoms in several such conditions is
sudden, with high morbidity and mortality rates. Awareness of the subject’s life-long risk for developing a genetic disorder enables
application of available preventive or alleviating medical interventions (e.g. dietary restrictions, specific drugs, surgery, surveillance). This article provides an overview of medically actionable monogenic disorders and their pre-symptomatic intervention options, distribution of secondary findings identified in exome datasets, as well as current international views and guidelines regulating their return to the patients.