Defining categories of actionability for secondary findings in next-generation sequencing

Area of Science:

• Clinical Genetics
• Bioethics
• Genomic Medicine

Background:

• Next-generation sequencing (NGS) is vital for diagnosing Mendelian diseases.
• NGS frequently yields secondary findings, complicating patient disclosure.
• Defining 'actionability' for secondary findings is crucial but inconsistently interpreted.

Purpose of the Study:

• To propose a practical framework for implementing the concept of actionability in returning secondary findings.
• To differentiate types of actionability to guide disclosure decisions.
• To explore the role of patient values and gene characteristics in determining actionability.

Main Methods:

• Conceptual analysis and framework development for actionability.
• Distinction of three tiers of actionability: medical actions, patient-initiated actions, and life-plan decisions.
• Discussion of ethical considerations, including patient autonomy and the return of uncertain findings.

Main Results:

• Actionability is contingent upon specific mutation/gene properties and individual patient values.
• Three distinct types of actionability were identified to guide disclosure.
• Patient autonomy influences decisions regarding the return of uncertain clinical significance variants.

Conclusions:

• A nuanced approach to actionability, integrating medical and personal factors, is essential for ethical secondary finding disclosure.
• Physicians must consider individual patient circumstances and values when discussing secondary findings.
• Refraining from returning uncertain genetic information may be ethically justifiable in certain contexts.