Article| Volume 24, ISSUE 6, P1306-1315, June 2022

The patient with 41 reports: Analysis of laboratory exome sequencing reporting of a “virtual patient”

  • Danya F. Vears
    Correspondence and requests for materials should be addressed to Danya F. Vears, Murdoch Children’s Research Institute, Royal Children's Hospital, 50 Flemington Road, Parkville 3052, Victoria, Australia
    Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia

    Melbourne Law School, The University of Melbourne, Carlton, Victoria, Australia

    Center for Biomedical Ethics and Law, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven, Leuven, Belgium

    Leuven Institute for Human Genetics and Society (LIGAS), KU Leuven, Leuven, Belgium
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  • Martin Elferink
    Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
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  • Marjolein Kriek
    Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
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  • Pascal Borry
    Center for Biomedical Ethics and Law, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven, Leuven, Belgium

    Leuven Institute for Human Genetics and Society (LIGAS), KU Leuven, Leuven, Belgium
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  • Koen L. van Gassen
    Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands
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Published:April 07, 2022DOI:



      Few studies have systematically analyzed the structure and content of laboratory exome sequencing reports from the same patient.


      We merged 8 variants from patients into “normal” exomes to create virtual patient–parent trios. We provided laboratories worldwide with the data and patient phenotype information (developmental delay, dysmorphic features, and cardiac hypertrophy). Laboratories analyzed the data and issued a diagnostic exome report. Reports were scored using a coding matrix developed from existing guidelines.


      In total, 41 laboratories representing 17 countries issued reports. Reporting of quality control statistics and technical information was poor (46.3%). Although 75.6% of the reports clearly stated the classification of all reported variants, few reports listed extensive evidence supporting variant classification. Only 53.1% of laboratories that reported unsolicited or secondary findings gave advice regarding health-related follow-up and 20.5% gave advice regarding cascade testing for relatives. Of the 147 variants reported, 105 (71.4%) were classified in agreement with classifications based on American College of Medical Genetics and Genomics/Association for Molecular Pathology and Association for Clinical Genomic Science guidelines. Concordance was higher for known pathogenic variants (86.3%) than for novel unpublished variants (56.8%).


      The considerable variability identified in the components that laboratories included in their reports and their classification of variants suggests that existing guidelines are not being used consistently with significant implications for patient care.


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