Challenges in returning results in a genomic medicine implementation study: the Return of Actionable Variants Empirical (RAVE) study

• Published in: Npj genomic medicine Vol. 5; no. 1; p. 19
• Main Authors: Kochan, David C, Winkler, Erin, Lindor, Noralane, Shaibi, Gabriel Q, Olson, Janet, Caraballo, Pedro J, Freimuth, Robert, Pacyna, Joel E, Breitkopf, Carmen Radecki, Sharp, Richard R, Kullo, Iftikhar J
• Format: Journal Article
• Language: English
• Published: England 04.05.2020
• ISSN: 2056-7944

To inform the process of returning results in genome sequencing studies, we conducted a quantitative and qualitative assessment of challenges encountered during the Return of Actionable Variants Empiric (RAVE) study conducted at Mayo Clinic. Participants (n = 2535, mean age 63 ± 7, 57% female) were sequenced for 68 clinically actionable genes and 14 single nucleotide variants. Of 122 actionable results detected, 118 were returnable; results were returned by a genetic counselor-86 in-person and 12 by phone. Challenges in returning actionable results were encountered in a significant proportion (38%) of the cohort and were related to sequencing and participant contact. Sequencing related challenges (n = 14), affecting 13 participants, included reports revised based on clinical presentation (n = 3); reports requiring corrections (n = 2); mosaicism requiring alternative DNA samples for confirmation (n = 3); and variant re-interpretation due to updated informatics pipelines (n = 6). Participant contact related challenges (n = 44), affecting 38 participants, included nonresponders (n = 20), decedents (n = 1), and previously known results (n = 23). These results should be helpful to investigators preparing for return of results in large-scale genomic sequencing projects.