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 - 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 -