Next-Generation Sequencing Germline Variant Confirmation
Summary of Recommendations
Recommendation Grading
Disclaimer
Overview
Title
Next-Generation Sequencing Germline Variant Confirmation
Authoring Organizations
Association for Molecular Pathology
National Society of Genetic Counselors
Publication Month/Year
May 17, 2023
Document Type
Guideline
Country of Publication
US
Document Objectives
Clinical laboratory implementation of next-generation sequencing (NGS)-based constitutional genetic testing has been rapid and widespread. In the absence of widely adopted comprehensive guidance, there remains substantial variability among laboratories in the practice of NGS. One issue of sustained discussion in the field is whether and to what extent orthogonal confirmation of genetic variants identified by NGS is necessary or helpful. The Association for Molecular Pathology Clinical Practice Committee convened the NGS Germline Variant Confirmation Working Group to assess current evidence regarding orthogonal confirmation and to establish recommendations for standardizing orthogonal confirmation practices to support quality patient care. Based on the results of a survey of the literature, a survey of laboratory practices, and subject expert matter consensus, eight recommendations are presented, providing a common framework for clinical laboratory professionals to develop or refine individualized laboratory policies and procedures regarding orthogonal confirmation of germline variants detected by NGS.
Inclusion Criteria
Male, Female, Adolescent, Adult, Child, Infant, Older adult
Health Care Settings
Ambulatory, Laboratory services
Intended Users
Genetics, nurse, nurse practitioner, physician, physician assistant
Scope
Assessment and screening
Diseases/Conditions (MeSH)
D017421 - Sequence Analysis
Keywords
Germline Testing, germline mutations, NGS, Next-Generation Sequencing, germline
Source Citation
Crooks KR, Farwell Hagman KD, Mandelker D, Santani A, Schmidt RJ, Temple-Smolkin RL, Lincoln SE. Recommendations for Next-Generation Sequencing Germline Variant Confirmation: A Joint Report of the Association for Molecular Pathology and National Society of Genetic Counselors. J Mol Diagn. 2023 May 17:S1525-1578(23)00103-4. doi: 10.1016/j.jmoldx.2023.03.012. Epub ahead of print. PMID: 37207865.
Supplemental Methodology Resources
Data Supplement, Data Supplement, Data Supplement, Data Supplement, Data Supplement