Document Type
Article
Original Publication Date
2017
Journal/Book/Conference Title
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
Volume
141
Issue
6
First Page
798
Last Page
805
DOI of Original Publication
10.5858/arpa.2016-0622-RA
Date of Submission
July 2017
Abstract
Context.-With the decrease in the cost of sequencing, the clinical testing paradigm has shifted from single gene to gene panel and now whole-exome and whole-genome sequencing. Clinical laboratories are rapidly implementing next-generation sequencing-based whole-exome and whole-genome sequencing. Because a large number of targets are covered by whole-exome and whole-genome sequencing, it is critical that a laboratory perform appropriate validation studies, develop a quality assurance and quality control program, and participate in proficiency testing.
Objective.-To provide recommendations for wholeexome and whole-genome sequencing assay design, validation, and implementation for the detection of germline variants associated in inherited disorders.
Data Sources.-An example of trio sequencing, filtration and annotation of variants, and phenotypic consideration to arrive at clinical diagnosis is discussed.
Conclusions.-It is critical that clinical laboratories planning to implement whole-exome and whole-genome sequencing design and validate the assay to specifications and ensure adequate performance prior to implementation. Test design specifications, including variant filtering and annotation, phenotypic consideration, guidance on consenting options, and reporting of incidental findings, are provided. These are important steps a laboratory must take to validate and implement whole-exome and whole-genome sequencing in a clinical setting for germline variants in inherited disorders.
Rights
Copyright © 2017 College of American Pathologists
Is Part Of
VCU Pathology Publications
Comments
Originally published at http://doi.org/10.5858/arpa.2016-0622-RA