Consultation informs strategies to improve functional evidence use in variant classification

Area of Science:

• Genetics
• Clinical Diagnostics
• Bioinformatics

Background:

• Variant classification is crucial for diagnosing genetic diseases.
• Experimental assay data offers strong evidence for variant pathogenicity but is underutilized.
• Applied genetics professionals face challenges in integrating functional evidence into clinical practice.

Purpose of the Study:

• To assess the application of functional evidence in variant classification by genetic diagnostic professionals in Australasia.
• To identify barriers and needs for improving the use of experimental assay data in clinical settings.

Main Methods:

• A survey was conducted among genetic diagnostic professionals in Australasia.
• The survey assessed confidence and practices regarding the use of functional evidence.
• Analysis focused on identifying needs for support resources and updated guidelines.

Main Results:

• Survey respondents expressed low confidence in applying functional evidence.
• Uncertainty regarding practice recommendations was a primary barrier.
• Professionals requested educational opportunities, expert recommendations, and updated guidelines.

Conclusions:

• There is a significant need to enhance the utilization of functional evidence in variant classification.
• Developing clear guidelines and providing expert recommendations are essential for improving diagnostic practice.
• A curated list of functional assays from expert panels serves as an initial step towards supporting evidence evaluation.