Thursday 28 January 2027  | 16:10 - 17:10 I Workshop Room

 

Variant interpretation is becoming increasingly complex. As genomic testing expands across healthcare and research, clinicians and scientists are identifying more rare and difficult to interpret variants than ever before.

Variants of uncertain significance (VUS) remain one of the greatest barriers to delivering timely diagnoses and actionable clinical decisions.

This interactive workshop will focus on the diagnostic value of variant interpretation, exploring how the field can move from identifying a variant to confidently understanding what it means and ultimately what action should be taken.

Participants will work through real interpretation challenges and consider how guidelines, prediction tools and collaborative genomic networks can together transform clinical decision-making.

Variant Interpretation

Workshop Leaders

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Speaker profile image for Joe Marsh

Joe Marsh

Professor and Personal Chair of Computational Protein Biology
University of Edinburgh
Speaker profile image for Marlen Lauffer

Marlen Lauffer

DRM Transition Research Fellow
University of Oxford
Speaker profile image for Miranda Durkie

Miranda Durkie

Consultant Clinical Scientist, Rare Disease Lead
North East Yorkshire Genomic Laboratory Hub
Speaker profile image for Emma-Jane Cassidy

Emma-Jane Cassidy

Principal Clinical Scientist in Rare Disease Genomics
NHS

What to expect

By the end of the workshop, participants will be able to: 

  • Understand how evolving interpretation guidelines influence diagnostic decision-making 

  • Evaluate the role of prediction models and functional evidence in resolving VUS 

  • Explore how national genomic networks can improve evidence sharing and interpretation consistency 

  • Identify practical opportunities to move from variant identification to clinically actionable interpretation. 

Who should attend

This workshop is designed for genomic clinicians, scientists, bioinformaticians and researchers involved in variant interpretation and rare disease diagnosis, including:

  • Clinical scientists & laboratory scientists
  • Genomic researchers & computational biologists
  • Bioinformaticians & data scientists
  • Functional genomics researchers
  • Rare disease researchers & translational scientists
  • Genomic medicine leaders & programme managers.

Event format

A 90-minute expert-led, case-based workshop combining short talks, hands-on variant interpretation exercises and group discussion.

Participants will work through real-world scenarios, apply interpretation approaches and discuss challenges with peers and expert speakers.

The format is designed to be practical, interactive and immediately applicable to participants' work.

Workshop Agenda

Part 1: Interpreting Variants Under Evolving Guidelines (25 minutes) 

This opening session will explore why variant interpretation frameworks are changing and what those changes mean in practice. 

Topics include: 

  • The growing challenge of VUS interpretation 

  • Why existing frameworks are under pressure 

  • Key developments in emerging ACMG guidance 

  • UK vs US approaches to variant interpretation 

  • How guideline changes may influence diagnostic confidence and clinical action 

Groups will consider: 

  • What classification would they assign today? 

  • Which evidence is most influential? 

  • Where does uncertainty remain? 

  • What additional evidence would most improve the interpretation? 

Miranda Durkie, Consultant Clinical Scientist, Rare Disease Lead, North East Yorkshire Genomic Laboratory Hub

Part 2: Prediction Models and Functional Evidence (25 minutes) 

This session will explore how computational prediction and functional genomics are reshaping variant interpretation. 

  • Machine learning approaches to variant effect prediction 

  • Multiplexed Assays of Variant Effect (MAVEs) 

  • Calibration of computational and functional evidence for clinical interpretation 

  • Integrating computational and functional evidence 

  • Strengths, limitations and sources of bias 

Groups will discuss: 

  • Does the new evidence change the classification? 

  • How strong is the computational or functional evidence? 

  • Is the evidence appropriately calibrated for this gene or variant? 

  • What evidence would be sufficient to reclassify a VUS? 

  • How should conflicting computational and functional evidence be handled? 

Joe Marsh, Professor of Computational Protein Biology at the Institute of Genetics and Cancer, University of Edinburgh

Part 3: The Genomic Network of Excellence and the Future of Interpretation (25 minutes)

This session will explore how collaborative genomic infrastructure can improve interpretation at scale.

Topics include: 

  • The role of the Genomic Network of Excellence 

  • National evidence sharing and data harmonisation 

  • Functional genomics infrastructure 

  • Cross-institutional collaboration 

  • Continuous updating of variant classifications 

  • Building a learning healthcare system for genomic interpretation 

Emma-Jane Cassidy, Principal Clinical Scientist in Rare Disease Genomics, NHS

Part 4: Assessing Genetic Diagnosis for Therapeutic Actionability (10 minutes)

Once a genetic diagnosis has been made, patients and families are left with one question: What’s next? In this section, we will explore what possibilities are available to treat individuals with genetic conditions and how it can be determined what is the best therapeutic approach.  

  • Overview of assessment of therapeutic actionability for pathogenic DNA variants  

  • Nationwide and global networks for establishing these assessments  

  • Guidelines and tools to perform actionability assessments  

  • UK Therapeutic Actionability Hub  

 Marlen Lauffer, IDRM Transition Research Fellow, University of Oxford 

**Please register your interest in being considered for a workshop place when completing your Festival ticket registration.**