Tiered Somatic Variant Classification Adoption Has Increased Worldwide With Some Practice Differences Based on...

Area of Science:

• Molecular Pathology
• Genomics
• Clinical Diagnostics

Background:

• The 2017 Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists (CAP) guideline standardizes somatic variant interpretation.
• Next-generation sequencing (NGS) is crucial for identifying these variants in clinical settings.

Purpose of the Study:

• To assess the adoption and performance of the 2017 tier classification guideline in laboratories performing somatic NGS.
• To identify areas for improvement in future guideline revisions.

Main Methods:

• A survey was distributed to laboratories participating in CAP proficiency testing for solid tumors (NGSST) and hematologic malignancies (NGSHM).
• Data collected included guideline usage, modifications, satisfaction, and perceived reproducibility.

Main Results:

• Over 64% of laboratories use tier classification systems, with 84.9% (NGSST) and 73.6% (NGSHM) using the 2017 guideline.
• Most users (over 70%) reported satisfaction and high reproducibility.
• Future revisions should consider variants for disease monitoring and germline variants.

Conclusions:

• The 2017 guideline shows significant adoption and user satisfaction in CAP-accredited laboratories.
• Modifications focusing on disease monitoring and germline variants could enhance the guideline's quality, reproducibility, and clinical utility.