Slice Testing-Considerations from Ordering to Reporting: A Joint Report of the Association for Molecular Pathology, College of American Pathologists, and National Society of Genetic Counselors

Jeffrey A SoRelle; Birgit H Funke; Celeste C Eno; Jianling Ji; Avni Santani; Pinar Bayrak-Toydemir; Megan Wachsmann; Karen E Wain; Rong Mao

doi:10.1016/j.jmoldx.2023.11.008

Slice Testing-Considerations from Ordering to Reporting: A Joint Report of the Association for Molecular Pathology, College of American Pathologists, and National Society of Genetic Counselors

J Mol Diagn. 2024 Mar;26(3):159-167. doi: 10.1016/j.jmoldx.2023.11.008. Epub 2023 Dec 14.

Authors

Jeffrey A SoRelle¹, Birgit H Funke², Celeste C Eno³, Jianling Ji⁴, Avni Santani⁵, Pinar Bayrak-Toydemir⁶, Megan Wachsmann⁷, Karen E Wain⁸, Rong Mao⁹

Affiliations

¹ Whole Exome Sequencing Standards Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Rockville, Maryland; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
² Whole Exome Sequencing Standards Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Rockville, Maryland; Sema4, Stamford, Connecticut; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
³ Whole Exome Sequencing Standards Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Rockville, Maryland; Department of Academic Pathology, Cedars-Sinai Medical Center, Los Angeles, California.
⁴ Whole Exome Sequencing Standards Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Rockville, Maryland; Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California; Department of Pathology, University of Southern California, Los Angeles, California.
⁵ Whole Exome Sequencing Standards Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Rockville, Maryland; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
⁶ Whole Exome Sequencing Standards Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Rockville, Maryland; Department of Pathology, University of Utah, Salt Lake City, Utah; ARUP Laboratories, Salt Lake City, Utah.
⁷ Whole Exome Sequencing Standards Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Rockville, Maryland; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas; VA North Texas Health Care System, Dallas, Texas.
⁸ Whole Exome Sequencing Standards Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Rockville, Maryland; GeneDx, LLC, Gaithersburg, Maryland.
⁹ Whole Exome Sequencing Standards Working Group of the Clinical Practice Committee, Association for Molecular Pathology, Rockville, Maryland; Department of Pathology, University of Utah, Salt Lake City, Utah; ARUP Laboratories, Salt Lake City, Utah. Electronic address: [email protected].

PMID: 38103592
DOI: 10.1016/j.jmoldx.2023.11.008

Abstract

As the number of genes associated with various germline disorders continues to grow, it is becoming more difficult for clinical laboratories to maintain separate assays for interrogating disease-focused gene panels. One solution to this challenge is termed slice testing, where capture backbone is used to analyze data specific to a set of genes, and for this article, we will focus on exome. A key advantage to this strategy is greater flexibility by adding genes as they become associated with disease or the ability to accommodate specific provider requests. Here, we provide expert consensus recommendations and results from an Association for Molecular Pathology-sponsored survey of clinical laboratories performing exome sequencing to compare a slice testing approach with traditional static gene panels and comprehensive exome analysis. We explore specific considerations for slices, including gene selection, analytic performance, coverage, quality, and interpretation. Our goal is to provide comprehensive guidance for clinical laboratories interested in designing and using slice tests as a diagnostic.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Counselors*
Humans
Pathologists
Pathology, Molecular*
Surveys and Questionnaires
United States