title: The Exome Clinic and the role of medical genetics expertise in the interpretation of exome sequencing results.
abstract: Evaluation of the clinician's role in the optimal interpretation of clinical exome sequencing (ES) results.
  
  
  
  Retrospective chart review of the first 155 patients who underwent clinical ES in our Exome Clinic and direct interaction with the ordering geneticist to evaluate the process of interpretation of results.
  
  
  
  The most common primary indication was neurodevelopmental problems (~66%), followed by multiple congenital anomalies (~10%). Based on sequencing data, the overall diagnostic yield was 36%. After assessment by the medical geneticist, incorporation of detailed phenotypic and molecular data, and utilization of additional diagnostic modalities, the final diagnostic yield increased to 43%. Seven patients in our cohort were included in initial case series that described novel genetic syndromes, and 23% of patients were involved in subsequent research studies directly related to their results or involved in efforts to move beyond clinical ES for diagnosis. Clinical management was directly altered due to the ES findings in 12% of definitively diagnosed cases.
  
  
  
  Our results emphasize the usefulness of ES, demonstrate the significant role of the medical geneticist in the diagnostic process of patients undergoing ES, and illustrate the benefits of postanalytical diagnostic work-up in solving the "diagnostic odyssey." Genet Med advance online publication 02 March 2017.
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Dustin
authors.identifier: 0000-0002-6027-6020
authors.initials: D
authors.lastname: Baldridge
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.|Current affiliation: Mercy Clinic-Kids Genetics, Mercy Children's Hospital St. Louis, St. Louis, Missouri, USA.
authors.forename: Jennifer
authors.identifier: 0000-0003-2114-8066
authors.initials: J
authors.lastname: Heeley
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Marisa
authors.identifier: 0000-0002-5448-1204
authors.initials: M
authors.lastname: Vineyard
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Manwaring
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Tomi L
authors.identifier: 0000-0002-1637-8310
authors.initials: TL
authors.lastname: Toler
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Emily
authors.identifier: 0000-0002-9783-0013
authors.initials: E
authors.lastname: Fassi
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Elise
authors.identifier: 0000-0002-1626-5009
authors.initials: E
authors.lastname: Fiala
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Brown
authors.affiliation: Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Goss
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Marcia
authors.initials: M
authors.lastname: Willing
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Grange
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.|Current affiliation: National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Kozel
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Marwan
authors.initials: M
authors.lastname: Shinawi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D059472:Exome; D005104:Expert Testimony; D005260:Female; D005817:Genetic Counseling; D030342:Genetic Diseases, Inborn / Q000175:diagnosis / Q000235:genetics; D005820:Genetic Testing; D005826:Genetics, Medical / Q000379:methods; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010820:Physicians; D012189:Retrospective Studies; D000073359:Exome Sequencing; D055815:Young Adult