A Framework of Critical Considerations in Clinical Exome Reanalyses by Clinical and Laboratory Standards Institute

Marco L. Leung, Jianling Ji, Samuel Baker, Jillian G. Buchan, Theru A. Sivakumaran, Bryan L. Krock, Rebecca Hutchins, Pinar Bayrak-Toydemir, John Pfeifer, Maria Laura Cremona, Birgit Funke, Avni B. Santani

Research output: Contribution to journalArticlepeer-review

Abstract

Exome reanalysis is useful for providing molecular diagnoses for previously uninformative samples. However, challenges exist in implementing a practical solution for clinicians and laboratories. This study complements the current literature by providing practical considerations for patient-level and cohort-level reanalyses. The Clinical and Laboratory Standards Institute assembled the Document Development Committee and an interpretation working group that developed the framework for reevaluation of exome-based data. We describe two distinct but complementary approaches toward exome reanalyses: clinician-initiated patient-level reanalysis, and laboratory-initiated cohort-level reanalysis. We highlight the advantages and constraints for both approaches, and provide a high-level conceptual guide for ordering clinicians and laboratories through the critical decision pathways. Because clinical exome sequencing continues to be the standard of care in genetics, exome reanalysis would be critical in increasing the overall diagnostic yield. A systematic guide will facilitate the efficient adoption of reevaluation of exome data for laboratories, health care professionals, genetic counselors, and clinicians.

Original languageEnglish
Pages (from-to)177-188
Number of pages12
JournalJournal of Molecular Diagnostics
Volume24
Issue number2
DOIs
StatePublished - Feb 2022

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