title: Actionable clinical decisions based on comprehensive genomic evaluation in asymptomatic adults.
abstract: Whole-exome sequencing (WES) arises as a new approach in diagnosing individuals affected by multigenic and complex phenotypes. Herein, we aim to examine whether WES is useful in screening asymptomatic individuals for actionable interventions, which has not yet been established. Twenty-five healthy adults underwent WES, bioinformatics, and manual curation of their exomes. Six participants (24%) harbored significant, management-changing variants in cancer predisposition genes, American College of Medical Genetics, and genomics reportable cardiac diseases and pharmacogenomic biomarkers that have led to clinical recommendations and interventions. Furthermore, more than 80% of the participants (21) carried 1-3 genetic variants with an associated clinical guideline for an altered drug dosing or administration based on the FDA's table of pharmacogenomics. These results support WES potential not only to answer specific diagnostic questions presented by the relevant personal and/or family history but also to uncover clinically important genetic findings unrelated to the primary indication for sequencing.
authors.affiliation: Faculty of Medicine, Tel Aviv University Tel Aviv, 69978, Israel.
authors.forename: Nir
authors.initials: N
authors.lastname: Pillar
authors.affiliation: Faculty of Medicine, Tel Aviv University Tel Aviv, 69978, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Isakov
authors.affiliation: Faculty of Medicine, Tel Aviv University Tel Aviv, 69978, Israel.
authors.forename: Daphna
authors.initials: D
authors.lastname: Weissglas-Volkov
authors.affiliation: Faculty of Medicine, Tel Aviv University Tel Aviv, 69978, Israel.
authors.forename: Shay
authors.initials: S
authors.lastname: Botchan
authors.affiliation: The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center Tel-Hashomer, Israel.
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.affiliation: The Integrated Cancer Prevention Center, Tel Aviv Medical Center, Tel Aviv University Tel Aviv, Israel.
authors.forename: Nadir
authors.initials: N
authors.lastname: Arber
authors.affiliation: Faculty of Medicine, Tel Aviv University Tel Aviv, 69978, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
keywords: Exome sequencing; clinical decision; genome; genomic