Hart MR, Biesecker BB, Blout CL, Christensen KD, Amendola LM, Bergstrom KL, et al. Secondary findings from clinical genomic sequencing: prevalence, patient perspectives, family history assessment, and health-care costs from a multisite study. Genet Med. 2019;21:1100–1110.

PubMed  Article  Google Scholar 

Johnston JJ, Rubinstein WS, Facio FM, Ng D, Singh LN, Teer JK, et al. Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes. Am J Hum Genet. 2012;91:97–108.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Katz AE, Nussbaum RL, Solomon BD, Rehm HL, Williams MS, Biesecker LG. Management of secondary genomic findings. Am J Hum Genet. 2020;107:3–14.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Sapp JC, Johnston JJ, Driscoll K, Heidlebaugh AR, Miren Sagardia A, Dogbe DN, et al. Evaluation of recipients of positive and negative secondary findings evaluations in a hybrid CLIA-research sequencing pilot. Am J Hum Genet. 2018;103:358–366.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013;15:565–574.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017;19:249–255.

PubMed  Article  Google Scholar 

Miller DT, Lee K, Chung WK, Gordon AS, Herman GE, Klein TE, et al. ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021 May 20; https://doi.org/10.1038/s41436-021-01172-3. Online ahead of print.

Christenhusz GM, Devriendt K, Dierickx K. To tell or not to tell? A systematic review of ethical reflections on incidental findings arising in genetics contexts. Eur J Hum Genet. 2013;21:248–255.

PubMed  Article  Google Scholar 

Jackson L, Goldsmith L, O’Connor A, Skirton H. Incidental findings in genetic research and clinical diagnostic tests: a systematic review. Am J Med Genet A. 2012;158a:3159–3167.

PubMed  Article  Google Scholar 

Mackley MP, Fletcher B, Parker M, Watkins H, Ormondroyd E. Stakeholder views on secondary findings in whole-genome and whole-exome sequencing: a systematic review of quantitative and qualitative studies. Genet Med. 2017;19:283–293.

PubMed  Article  Google Scholar 

Ormond KE, O’Daniel JM, Kalia SS. Secondary findings: How did we get here, and where are we going? J Genet Couns. 2019;28:326–333.

PubMed  Article  Google Scholar 

Bertier G, Hétu M, Joly Y. Unsolved challenges of clinical whole-exome sequencing: a systematic literature review of end-users’ views. BMC Med Genomics. 2016;9:52.

PubMed  PubMed Central  Article  Google Scholar 

de Wert G, Dondorp W, Clarke A, Dequeker E, Cordier C, Deans Z, et al. Opportunistic genomic screening. Recommendations of the European Society of Human Genetics. Eur J Hum Genet. 2021;29:365–377.

PubMed  Article  Google Scholar 

Delanne J, Nambot S, Chassagne A, Putois O, Pelissier A, Peyron C, et al. Secondary findings from whole-exome/genome sequencing evaluating stakeholder perspectives. A review of the literature. Eur J Med Genet. 2019;62:103529.

CAS  PubMed  Article  Google Scholar 

Salari P, Larijani B. Ethical issues surrounding personalized medicine: a literature review. Acta Med Iran. 2017;55:209–217.

PubMed  Google Scholar 

All of Us Research Program I, Denny JC, Rutter JL, Goldstein DB, Philippakis A, Smoller JW, et al. The “All of Us” Research Program. N Engl J Med. 2019;381:668–676.

Article  Google Scholar 

Kaye J, Hurles M, Griffin H, Grewal J, Bobrow M, Timpson N, et al. Managing clinically significant findings in research: the UK10K example. Eur J Hum Genet. 2014;22:1100–1104.

PubMed  PubMed Central  Article  Google Scholar 

Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–269.

Booth A, Papaioannou D, Sutton A. Systematic approaches to a sucessful literature review. Thousand Oaks, CA: SAGE publications; 2012.

Gale NK, Heath G, Cameron E, Rashid S, Redwood S. Using the framework method for the analysis of qualitative data in multi-disciplinary health research. BMC Med Res Methodol. 2013;13:117.

PubMed  PubMed Central  Article  Google Scholar 

Baldridge D, Heeley J, Vineyard M, Manwaring L, Toler TL, Fassi E, et al. The Exome Clinic and the role of medical genetics expertise in the interpretation of exome sequencing results. Genet Med. 2017;19:1040–1048.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Basel D, McCarrier J. Ending a diagnostic odyssey: family education, counseling, and response to eventual diagnosis. Pediatr Clin North Am. 2017;64:265–272.

PubMed  Article  Google Scholar 

Catenacci DV, Amico AL, Nielsen SM, Geynisman DM, Rambo B, Carey GB, et al. Tumor genome analysis includes germline genome: are we ready for surprises? Int J Cancer. 2015;136:1559–1567.

CAS  PubMed  Article  Google Scholar 

Chirita-Emandi A, Andreescu N, Zimbru CG, Tutac P, Arghirescu S, Serban M, et al. Challenges in reporting pathogenic/potentially pathogenic variants in 94 cancer predisposing genes - in pediatric patients screened with NGS panels. Sci Rep. 2020;10:223.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Helm BM, Langley K, Spangler BB, Schrier, Vergano SA. Military health care dilemmas and genetic discrimination: a family’s experience with whole exome sequencing. Narrat Inq Bioeth. 2015;5:179–186.

PubMed  Article  Google Scholar 

Pendrick DM, Oberg JA, Hsiao SJ, Chung WK, Koval C, Sireci A, et al. Identification of a secondary RET mutation in a pediatric patient with relapsed acute myeloid leukemia leads to the diagnosis and treatment of asymptomatic metastatic medullary thyroid cancer in a parent: a case for sequencing the germline. Cold Spring Harb Mol Case Stud. 2019;5:a003889.

Leppig KA, Thiese HA, Carrel D, Crosslin DR, Dorschner MO, Gordon AS, et al. Building a family network from genetic testing. Mol Genet Genomic Med. 2017;5:122–129.

PubMed  Article  Google Scholar 

You YN, Borras E, Chang K, Price BA, Mork M, Chang GJ, et al. Detection of pathogenic germline variants among patients with advanced colorectal cancer undergoing tumor genomic profiling for precision medicine. Dis Colon Rectum. 2019;62:429–437.

PubMed  PubMed Central  Article  Google Scholar 

Hao J, Hassen D, Manickam K, Murray MF, Hartzel DN, Hu Y, et al. Healthcare utilization and costs after receiving a positive BRCA1/2 result from a genomic screening program. J Pers Med. 2020;10:7.

Haukkala A, Kujala E, Alha P, Salomaa V, Koskinen S, Swan H, et al. The return of unexpected research results in a biobank study and referral to health care for heritable long QT syndrome. Public Health Genomics. 2013;16:241–250.

CAS  PubMed  Article  Google Scholar 

Horiuchi Y, Matsubayashi H, Kiyozumi Y, Nishimura S, Higashigawa S, Kado N, et al. Disclosure of secondary findings in exome sequencing of 2480 Japanese cancer patients. Hum Genet. 2021;140:321–331.

Lewis KL, Hooker GW, Connors PD, Hyams TC, Wright MF, Caldwell S, et al. Participant use and communication of findings from exome sequencing: a mixed-methods study. Genet Med. 2016;18:577–583.

CAS  PubMed  Article  Google Scholar 

Schwartz MLB, McCormick CZ, Lazzeri AL, Lindbuchler DM, Hallquist M, Manickam K, et al. A model for genome-first care: returning secondary genomic findings to participants and their healthcare providers in a large research cohort. Am J Hum Genet. 2018;103:328–337.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Thompson ML, Finnila CR, Bowling KM, Brothers KB, Neu MB, Amaral MD, et al. Genomic sequencing identifies secondary findings in a cohort of parent study participants. Genet Med. 2018;20:1635–1643.

PubMed  PubMed Central  Article  Google Scholar 

CSER Consortium. https://cser-consortium.org. Accessed 5 January 2021.

Amendola LM, Lautenbach D, Scollon S, Bernhardt B, Biswas S, East K, et al. Illustrative case studies in the return of exome and genome sequencing results. Per Med. 2015;12:283–295.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Mackley M, McGuire K, Taylor J, Watkins H, Ormondroyd E. From genotype to phenotype. Circ Genom Precis Med. 2018;11:e002316.

PubMed  PubMed Central  Article  Google Scholar 

Nestor JG, Marasa M, Milo-Rasouly H, Groopman EE, Husain SA, Mohan S, et al. Pilot study of return of genetic results to patients in adult nephrology. Clin J Am Soc Nephrol. 2020;15:651–664.

CAS  PubMed  PubMed Central  Article  Google Scholar 

Papaz T, Liston E, Zahavich L, Stavropoulos DJ, Jobling RK, Kim RH, et al. Return of genetic and genomic research findings: experience of a pediatric biorepository. BMC Med Genomics. 2019;12:173.

PubMed  PubMed Central  Article  Google Scholar 

Rego S, Dagan-Rosenfeld O, Bivona SA, Snyder MP, Ormond KE. Much ado about nothing: a qualitative study of the experiences of an average-risk population receiving results of exome sequencing. J Genet Couns. 2019;28:428–437.

PubMed  PubMed Central  Article  Google Scholar 

Rego S, Dagan-Rosenfeld O, Zhou W, Sailani MR, Limcaoco P, Colbert E, et al. High-frequency actionable pathogenic exome variants in an average-risk cohort. Cold Spring Harb Mol Case Stud. 2018;4:a003178.

Westphal DS, Leszinski GS, Rieger-Fackeldey E, Graf E, Weirich G, Meitinger T, et al. Lessons from exome sequencing in prenatally diagnosed heart defects: a basis for prenatal testing. Clin Genet. 2019;95:582–589.

CAS  PubMed  Article  Google Scholar 

Wynn J, Martinez J, Bulafka J, Duong J, Zhang Y, Chiuzan C, et al. Impact of receiving secondary results from genomic research: a 12-month longitudinal study. J Genet Couns. 2018;27:709–722.

PubMed  Article  Google Scholar 

Ormondroyd E, Harper AR, Thomson KL, Mackley MP, Martin J, Penkett CJ, et al. Secondary findings in inherited heart conditions: a genotype-first feasibility study to assess phenotype, behavioural and psychosocial outcomes. Eur J Hum Genet. 2020;28:1486–1496.

PubMed  PubMed Central  Article  Google Scholar 

Lee K, Berg JS, Milko L, Crooks K, Lu M, Bizon C, et al. High diagnostic yield of whole exome sequencing in participants with retinal dystrophies in a clinical ophthalmology setting. Am J Ophthalmol. 2015;160:354–363.e359.