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

David C. Kochan, Erin Winkler, Noralane Lindor, Gabriel Q. Shaibi, Janet Olson, Pedro J. Caraballo, Robert Freimuth, Joel E. Pacyna, Carmen Radecki Breitkopf, Richard R. Sharp, Iftikhar J. Kullo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number19
Journalnpj Genomic Medicine
Volume5
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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