Approaching the Hard-to-Diagnose

Welcome to the Approaching the Hard-to-Diagnose course—a comprehensive and case-driven program designed for clinicians, medical geneticists, and healthcare professionals ready to go beyond the basics of genetic testing. If you've ever faced uncertainty when interpreting complex genetic findings or wondered how to make sense of a VUS result, this course is for you.

We know the world of rare disease diagnosis is often filled with uncertainty. Tests come back inconclusive, and traditional methods sometimes miss what really matters. That’s why this course focuses on real-life clinical complexities that arise even after the initial sequencing is done.

In this course, you’ll explore:

When to choose exome vs. genome sequencing, and how to recognize their unique strengths and limitations.
Interpretation of deep intronic variants, CNVs, and SVs using advanced tools like SpliceAI and integrated databases.
How to evaluate and follow up on VUS (Variants of Uncertain Significance) with practical frameworks and ongoing care strategies.
Reanalysis techniques and the role of novel gene discovery, particularly in unsolved rare disease cases.
Emerging technologies such as long-read sequencing (LRS) and RNA-seq, and how they are transforming the field of clinical genomics.

Every session is structured around clinical case examples, designed to mirror real-world diagnostic dilemmas you’ll encounter in practice. You won’t just learn about rare disease genomics—you’ll learn how to apply that knowledge, critically think through complex results, and participate more actively in your multidisciplinary care team.

Whether you’re in pediatrics, neurology, internal medicine, or genetics, this course will sharpen your diagnostic thinking and empower you to make more confident decisions when ordering, interpreting, and following up on advanced genetic tests.

Join us, and take one step closer to delivering precision care for patients with rare and undiagnosed conditions.

What's inside

Learning objectives

Understand how to choose between exome and genome testing based on clinical context and limitations.
Interpret complex variants such as deep intronic mutations, cnvs, and structural variants using advanced tools.
Evaluate and manage vus (variants of uncertain significance) with real-life decision-making strategies.
Apply strategies for reanalysis and novel gene discovery in unresolved cases.

Gain foundational knowledge of long-read sequencing and rna sequencing technologies.
Review advanced case examples that integrate complex variant interpretation and diagnostic strategy.
Build clinical confidence in tackling unsolved rare disease cases using cutting-edge genomic approaches.

Understand how to choose between exome and genome testing based on clinical context and limitations.
Interpret complex variants such as deep intronic mutations, cnvs, and structural variants using advanced tools.
Evaluate and manage vus (variants of uncertain significance) with real-life decision-making strategies.
Apply strategies for reanalysis and novel gene discovery in unresolved cases.
Gain foundational knowledge of long-read sequencing and rna sequencing technologies.
Review advanced case examples that integrate complex variant interpretation and diagnostic strategy.
Build clinical confidence in tackling unsolved rare disease cases using cutting-edge genomic approaches.