TY - JOUR
T1 - Challenges in returning results in a genomic medicine implementation study
T2 - the Return of Actionable Variants Empirical (RAVE) study
AU - Kochan, David C.
AU - Winkler, Erin
AU - Lindor, Noralane
AU - Shaibi, Gabriel Q.
AU - Olson, Janet
AU - Caraballo, Pedro J.
AU - Freimuth, Robert
AU - Pacyna, Joel E.
AU - Breitkopf, Carmen Radecki
AU - Sharp, Richard R.
AU - Kullo, Iftikhar J.
N1 - Funding Information:
The authors dedicate this research study to the late C.R.B. This study was funded by the NHGRI-supported eMERGE (Electronic Records and Genomics) Network (U01HG006379), NHLBI grant K24 HL137010 and UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS). We would also like to acknowledge Teresa Kruisselbrink, Nicole Bertsch, and Katherine Agre for providing genetic counseling support, Therese Hughes and Cori Berg for their assistance contacting medical providers, Jeremy Smith and Sara Snipes for study coordination, and Rick Kiefer and Arvid Nass for developing and parsing inbox messages.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41525-020-0127-2
DO - 10.1038/s41525-020-0127-2
M3 - Article
AN - SCOPUS:85084189124
SN - 2056-7944
VL - 5
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 19
ER -