Secondary findings (SFs) are present in 1–4% of individuals undergoing genome/exome sequencing. A review of how SFs are disclosed and what outcomes result from their receipt is urgent and timely.
We conducted a systematic literature review of SF disclosure practices and outcomes after receipt including cascade testing, family and provider communication, and health-care actions. Of the 1,184 nonduplicate records screened we summarize findings from 27 included research articles describing SF disclosure practices, outcomes after receipt, or both.
The included articles reported 709 unique SF index recipients/families. Referrals and/or recommendations were provided 647 SF recipients and outcome data were available for 236. At least one recommended evaluation was reported for 146 SF recipients; 16 reports of treatment or prophylactic surgery were identified. We found substantial variations in how the constructs of interest were defined and described.
Variation in how SF disclosure and outcomes were described limited our ability to compare findings. We conclude the literature provided limited insight into how the American College of Medical Genetics and Genomics (ACMG) guidelines have been translated into precision health outcomes for SF recipients. Robust studies of SF recipients are needed and should be prioritized for future research.
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The submitted manuscript (including supplemental information) includes all data analyzed during this review.
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This study was supported by National Institutes of Health (NIH) grant HG200387-07. The authors are grateful to Alexandra Gomes and Elaine Sullor at George Washington University for their assistance with preliminary search strategies, M. Anna Buser and Jennifer Johnston for their critical review of the manuscript, and Darryl Leja for graphics support.
Conceptualization: J.C.S, K.L.L., P.v.d.W., D.C. Data curation: J.C.S, F.M.F. Formal analysis: J.C.S, F.M.F., E.M. Funding acquisition: L.G.B. Investigation: J.C.S, F.M.F., D.C., E.M. Methodology: J.C.S, D.C. Project administration: J.C.S, L.G.B. Resources: L.G.B. Supervision: J.C.S., P.v.d.W., L.G.B. Validation: J.C.S., F.M.F., D.C., K.L.L. Writing—original draft: J.C.S, F.M.F. Writing—reviewing & editing: J.C.S, K.L.L. F.M.F., P.v.d.W., D.C., E.M., L.G.B.
L.G.B. is an uncompensated member of the Illumina Medical Ethics Committee, receives in-kind research support from Merck and Novartis, and honoraria from Cold Spring Harbor Press. The other authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Sapp, J.C., Facio, F.M., Cooper, D. et al. A systematic literature review of disclosure practices and reported outcomes for medically actionable genomic secondary findings. Genet Med (2021). https://doi.org/10.1038/s41436-021-01295-7