Exome Testing for Diagnosis (CNE)

Precision Medicine for Your Practice is a series of short (30 min), online modules covering specific topics in genomics and precision medicine. In this module, Exome Testing for Diagnosis, learn how to collaborate with both patients and genetic specialists around exome testing. This module will help primary care providers and other specialists identify patients who may benefit from exome testing, talk with patients and families about exome testing to support them in their decisions about genetic counseling and genetic testing, recognize clinically significant exome test results for use in patient care, and collaborate with genetic experts in ongoing patient management and evaluation. There are five parts of the module: overview via an animated video; practice cases to facilitate learning-by-doing; "dig deeper" for more in-depth topics; and logistics and additional resources for more detail.

To claim credit, follow the steps in the learning path.

CNE Disclosures

Activity Overview
Precision Medicine for Your Practice: Exome Testing for Diagnosis (CNE)

Original Publication Date:  October 31, 2018
Renewal Date: September 14, 2022
Expiration Date: September 14, 2024

Learning Outcome
Upon completion of this educational activity, the learner will be able to:

• Communicate with patients about decisions for exome testing, the impact of exome test results, and consultation with a genetic expert. 

Target Audience
This activity is designed to meet the educational needs of practicing nurses, advance practice nurses, physicians and physician assistants who provide primary care.

CNE Approval Statement

The Jackson Laboratory is co-providing this continuing nursing education activity with the American Medical Association and Scripps Health. This continuing nursing professional development activity was approved by the Northeast Multistate Division Education Unit, an accredited approver by the American Nurses Credentialing Center’s Commission on Accreditation.

In order to claim credit 1) answer the pre-assessment questions, 2) work through the module content in its entirety, 3) successfully complete the post-assessment answering 4 out of 5 questions correctly and 4) complete the evaluation. 

Nurses are eligible for a maximum of .50 contact hours upon the completion of this activity.

Planning Committee

• Emily Edelman, MS, CGC, Director, Clinical Education, The Jackson Laboratory
• Therese Ingram, MA, Associate Director and Senior Instructional Designer/Technologist, Clinical Education, The Jackson Laboratory
• Laura Nicholson, MD, PhD, Director of Research, Graduate Medical Education (GME), Scripps Health
• Kate Reed, MPH, ScM, CGC, Director, Precision Oncology Education, Clinical Education, The Jackson Laboratory
• Linda Steinmark, MS, CGC, Project Manager, Clinical Education, The Jackson Laboratory
• Janet K. Williams, PhD, RN, FAAN, Professor of Nursing, Chair of Behavioral and Social Science Research, University of Iowa

Faculty and Authors

• Emily Edelman, MS, CGC, Director, Clinical Education, The Jackson Laboratory (Author)
• Therese Ingram, MA, Associate Director and Senior Instructional Designer/Technologist, Clinical Education, The Jackson Laboratory (Author)
• Kate Reed, MPH, ScM, CGC, Director, Precision Oncology Education, Clinical Education, The Jackson Laboratory (Author)
• Linda Steinmark, MS, CGC, Project Manager, Clinical Education, The Jackson Laboratory (Author)

Subject Matter Experts

• Carolyn Applegate, MS, CGC, Johns Hopkins School of Medicine (Content Expert)

Conflict of Interest Disclosure
Unless otherwise noted, the program planners and faculty do not have a financial interest/arrangement or affiliation with any organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this course. All educational material has been peer-reviewed by external reviewers to assess for bias.

The following disclosures are reported that could be perceived as a real or apparent conflict of interest in the education program:

Janet K. Williams, PhD, RN, FAAN, stockholder of Pfizer. In her role as a planner, Dr. Williams recused herself from all deliberations relating to content related to the commercial entities with which she has a financial interest and is not responsible for reviewing for bias any related content. 

In 2020 Ms. Edelman received salary support through a proposal selected by the American Community Cancer Centers and Pfizer for an education project. In her roles as a planner and author, Ms. Edelman recused herself from all deliberations relating to content related to the commercial entity with which she has financial interest and was not responsible for reviewing for bias any related content. 

References

Alfares A, Aloraini T, Subaie LA, et al. Whole-genome sequencing offers additional but limited clinical utility compared with reanalysis of whole-exome sequencing. Genet Med. 2018; 20(11):1328-1333.

Biesecker LG, Green RC. Diagnostic Clinical Genome and Exome Sequencing. N Engl J Med. 2014; 370(25):2418-2425.

Bowdin S, Gilbert A, Bedoukian E, et al. Recommendations for the integration of genomics into clinical practice. Genet Med. 2016; 18(11):1075-1084.

Burdick KJ, Cogan JD, Rives LC, et al. Limitations of exome sequencing in detecting rare and undiagnosed diseases. Am J Med Genet A. 2020; 182(6):1400-1406.

Bush LW, Beck AE, Biesecker LG, et al. Professional responsibilities regarding the provision, publication, and dissemination of patient phenotypes in the context of clinical genetic and genomic testing: points to consider—a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2018; 20(2):169-171.

Deignan JL, Chung WK, Kearney HM, Monaghan KG, Rehder CW, Chao EC. Points to consider in the reevaluation and reanalysis of genomic test results: a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2019; 21(6):1267-1270.

Delaney SK, Hultner ML, Jacob HJ, et al. Toward clinical genomics in everyday medicine: perspectives and recommendations. Expert Review of Molecular Diagnostics. 2016; 16(5):521-532.

Evers C, et al. Impact of clinical exomes in neurodevelopmental and neurometabolic disorders. Mol Genet Metab. 2017 Aug;121(4):297-307. 

Ewans, L. J., et al. (2018). Whole-exome sequencing reanalysis at 12 months boosts diagnosis and is cost-effective when applied early in Mendelian disorders. Genet Med. 2018; 20(12):1564-1574. 

Frésard L, Montgomery SB. Diagnosing rare diseases after the exome. Cold Spring Harb Mol Case Stud. 2018; 4(6):a003392. 

Fung JLF, Yu MHC, Huang S, et al. A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis. NPJ Genom Med. 2020; 5:37.

Hopkins MK, Dugoff L, Kuller JA. Exome Sequencing and Its Emerging Role in Prenatal Genetic Diagnosis. Obstet Gynecol Surv. 2020; 75(5):317-320.

Kingsmore SF, Cakici JA, Clark MM, et al. A Randomized, Controlled Trial of the Analytic and Diagnostic Performance of Singleton and Trio, Rapid Genome and Exome Sequencing in Ill Infants. Am J Hum Genet. 2019; 105(4):719-733.

Liu P, Meng L, Normand EA, et al. Reanalysis of Clinical Exome Sequencing Data. N Engl J Med. 2019; 380(25):2478-2480.

Lord J, McMullan DJ, Eberhardt RY, et al. Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lancet. 2019; 393(10173):747-757.

Manickam, K., McClain, M. R., Demmer, L. A., et al. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021; Advance online publication.

Nambot, S., et al. Clinical whole-exome sequencing for the diagnosis of rare disorders with congenital anomalies and/or intellectual disability: substantial interest of prospective annual reanalysis. Genet Med. 2018; 20(6):645-654. 

Nolan D, Carlson M. Whole Exome Sequencing in Pediatric Neurology Patients. J Child Neurol. 2016; 31(7):887-894.

Pena LDM, Jiang Y, Schoch K, et al. Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases. Genet Med. 2018; 20(4):464-469.

Posey JE, Rosenfeld JA, James RA, et al. Molecular diagnostic experience of whole-exome sequencing in adult patients. Genet Med. 2016; 18(7):678-685.

Retterer K, Juusola J, Cho MT, et al. Clinical application of whole-exome sequencing across clinical indications. Genet Med. 2015; 18(7):696-704.

Rexach J, Lee H, Martinez-Agosto JA, et al. Clinical application of next generation sequencing to the practice of neurology. Lancet Neurol. 2019; 18(5):492–503.

Salfati, E. L., et al. Re-analysis of whole-exome sequencing data uncovers novel diagnostic variants and improves molecular diagnostic yields for sudden death and idiopathic diseases. Genome Med. 2019; 11(1):83.

Sawyer S, Hartley T, Dyment D, et al. Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care. Clin Genet. 2016; 89(3):275-284.

Shashi V, Schoch K, Spillmann R, et al. A comprehensive iterative approach is highly effective in diagnosing individuals who are exome negative. Genet Med. 2019; 21(1):161-172.

Tolusso, L. K., Hazelton, P., Wong, B., & Swarr, D. T. Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes. Genet Med. 2021; 23(5), 909–917.

Trosman JR, Weldon CB, Slavotinek A, Norton ME, Douglas MP, Phillips KA. Perspectives of US private payers on insurance coverage for pediatric and prenatal exome sequencing: Results of a study from the Program in Prenatal and Pediatric Genomic Sequencing (P3EGS). Genet Med. 2020; 22(2):283-291.

Walser SA, Werner-Lin A, Mueller R, Miller VA, Biswas S, Bernhardt BA. How do providers discuss the results of pediatric exome sequencing with families? Personalized Medicine. 2017; 14(5):409-422.

Wenger AM, Guturu H, Bernstein JA, Bejerano G. Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers. Genet Med. 2016; 19(2):209-214.

Wynn J, Ottman R, Duong J, et al. Diagnostic exome sequencing in children: A survey of parental understanding, experience and psychological impact. Clin Genet. 2018; 93(5):1039-1048.

Yang Y, Muzny DM, Xia F, et al. Molecular Findings Among Patients Referred for Clinical Whole-Exome Sequencing. JAMA. 2014; 312(18):1870.

Hardware/Software Requirements
Audio speakers or headphones
Screen resolution of 800X600 or higher
Adobe Reader 5.0 or higher 

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Should you have technical questions or questions regarding the content of the activity, please email Clinical and Continuing Education at the Jackson Laboratory.

Disclaimer 
All information in Precision Medicine for Your Practice is provided for educational purposes only. This information is not a substitute for clinical guidance or the consultation of a medical professional. Always seek the advice of a qualified health professional with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in Precision Medicine for Your Practice. Reliance on any information in Precision Medicine for Your Practice is solely at your own risk. The Jackson Laboratory does not endorse or recommend any specific procedures, tests, products, services, health professionals or other information that may be found in Precision Medicine for Your Practice.