Abstract
Purpose
Few studies have systematically analyzed the structure and content of laboratory exome
sequencing reports from the same patient.
Methods
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.
Results
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variants (86.3%) than for novel unpublished variants (56.8%).
Conclusion
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.
Keywords
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Article info
Publication history
Published online: April 07, 2022
Accepted:
March 3,
2022
Received in revised form:
February 27,
2022
Received:
September 8,
2021
Identification
Copyright
© 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
