Grant Number:	1R01CA304065-01 Interpret this number
Primary Investigator:	Makhnoon, Sukh
Organization:	Ut Southwestern Medical Center
Project Title:	Developing Consensus on a Practical Framework for Variant Reclassification and Recontact
Fiscal Year:	2025

PROJECT SUMMARY/ABSTRACT Over a 5–10-year period, between 6% and 15% of germline variants undergo reclassification, a process by which the clinical meaning of a given variant is recategorized based on updated evidence. Accurate and definitive variant classification is a critical component of clinical genetic testing, especially as test indications have broadened over time and more genes are being interrogated per test. Reclassification occurs frequently in clinical practice today and has well-demonstrated clinical utility. While consensus exists about the importance of and need for guidance regarding variant reinterpretation, reclassification, and patient recontact, the field of medical genetics is ablaze with debates over the nature and extent of stakeholder responsibilities on these issues. We propose to use deliberative research to construct a framework of principles that can provide practical guidance for ongoing policy development as genomic science evolves. Our research is directly responsive to numerous calls to action to develop standardized processes and guidelines in reinterpretation, reclassification, and recontact. We will achieve our goals through the following aims: Aim 1: Explore stakeholders’ views (and prime them) regarding key questions related to variant reinterpretation, reclassification, and recontact. Aim 2: Identify underlying values and principles and clarify areas of agreement and disagreement among stakeholder groups. Aim 3: Develop expert consensus on proposed solutions to the key questions. The proposed project will utilize a complementary set of methodologies to provide a comprehensive overview of variant RRR (Aims 1 and 2); a durable framework of practical principles (Aim 2) to guide future policy as genetic knowledge evolves; and a set of concrete, expert-derived policy recommendations (Aim 3). Generation of a durable framework of principles that can guide ongoing policy development in medical genetics – rather than a set of policy recommendations with limited shelf-life- is an important innovative element of the proposed work.





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