Why Interpreting Genetic Variants—Not Just Finding Them—Is Key to Faster Answers for Rare Diseases

A Conversation with Dr. Bob Daber, Vice President of Science and Technology Development at Labcorp 

Rare diseases affect hundreds of millions of people worldwide, yet for many patients and families, getting an accurate diagnosis remains a long and frustrating journey. In a recent STAT article, Dr. Bob Daber, vice president of science and technology development at Labcorp, explored why genetic variant interpretation—at scale—is one of the most critical drivers of progress in rare disease diagnosis and treatment. 

In this Q&A, Daber expands on that perspective, explaining what high-quality interpretation entails, why scale is essential, and how Labcorp applies data, technology, and scientific rigor to deliver faster, more meaningful answers for patients and providers. 

Q1: In your STAT article, you emphasize that genetic testing alone isn’t enough. Why is interpretation the real differentiator in rare disease? 

Dr. Bob Daber: 

A genetic test result without a complex underlying interpretation framework is just data—it’s not an answer. Every individual carries millions of genetic variants, and determining which are clinically meaningful is a complex scientific process, not a binary decision. 

At Labcorp, interpretation is a rigorous, multi-step scientific process that goes far beyond categorizing variants as benign or pathogenic. Each variant is evaluated using peer-reviewed literature, population frequency data, phenotypic correlations, functional evidence, inheritance patterns, and expert clinical judgment. Our AI-enabled tools, including Moon™, help prioritize and analyze variants at scale, while Apollo™, our continuously curated gene-phenotype knowledge base, provides critical clinical context. Importantly, interpretation is not static—variants are re-evaluated as new evidence emerges under the oversight of expert scientists and board-certified genetic counselors, ensuring that classifications remain accurate, transparent, and clinically meaningful. 

That depth and rigor are what turn sequencing results into something clinicians and families can use. 

Q2: Rare disease patients often experience long diagnostic odysseys. Where do those delays typically come from? 

Dr. Bob Daber:   

Delays in rare disease diagnosis are rarely due to a single factor. More often, they reflect a combination of barriers that compound over time—what I think of as a trifecta of awareness, access, and actionability. 

First, let’s address awareness. Many providers, especially at the earliest points in a patient’s journey, may not immediately recognize when a condition could have a genetic basis. As a result, genetic testing is often introduced late—after years of specialist visits and invasive or inconclusive tests. 

Second is the barrier of access. Even when genetic testing is clinically appropriate, reimbursement can be particularly confusing. Patients may hesitate to pursue testing out of concern that it won’t be covered by insurance, leaving them with an unexpected financial burden. That’s one of the reasons we work with payors, biopharma partners, and providers to offer sponsored testing programs—to help remove financial and logistical barriers and give patients earlier access to testing. 

Finally, there’s actionability. A genetic result is meaningful only if it can be interpreted and applied to patient care. Variants of uncertain significance can delay clarity if they can’t be resolved, which is why variant interpretation at scale is so critical. Equally important is genetic counseling, which helps providers and patients understand results and translate them into informed care decisions. 

When awareness, access, and actionability are addressed together, we can significantly shorten diagnostic odysseys and help patients reach answers sooner. 

Q3: You often talk about “interpretation at scale.” What does scale actually enable that smaller efforts cannot? 

Dr. Bob Daber:  

Scale transforms interpretation from a one-time assessment into a continuously learning system. At Labcorp, we’ve conducted millions of genetic tests and contributed more than 1.7 million variant classifications to ClinVar, making us among the most significant contributors globally.  This volume of testing on affected patients creates a large dataset which enables us to identify patterns across populations, validate findings more quickly, and reclassify variants as new evidence emerges, often resolving uncertainty for patients whose results might otherwise have remained inconclusive in smaller datasets or datasets comprised of primarily healthy individuals. 

Because we interpret variants across a large and diverse dataset, no single case stands alone. Each interpretation strengthens the knowledge base, improving accuracy and speed for future patients. That’s how variants of uncertain significance can be resolved over time, benefiting not just one family but many. 

Q4: How do AI-enabled tools like Moon™ fit into the interpretation workflow? 

Dr. Bob Daber: 

Machine learning -powered software weighs clinical and genetic information to identify the variants most relevant to each person’s case.  Moon™ allows us to scale without sacrificing quality. It rapidly analyzes tens of thousands of variants, prioritizes those most likely to be relevant, and surfaces connections that would be extremely difficult to identify manually. Apollo™ complements this by continuously linking genetic variants to evolving phenotype knowledge. 

But AI doesn’t replace scientific judgment. Our models are trained on high-quality data and undergo expert review. Board-certified genetic counselors and scientists remain central to the process, ensuring that interpretations are clinically sound, transparent, and actionable. 

Q5: Rare Disease Month often focuses on awareness. Where should the conversation go next? 

Dr. Bob Daber: 

Awareness is essential, but real progress happens through access. That includes access to testing, interpretation, and downstream care.  Genetic testing access programs, both pharma-led and those offered by Invitae, help to remove financial barriers, enabling eligible patients to receive testing that might otherwise be out of reach. 

Equally important is ensuring that results contribute to shared scientific resources. By submitting interpretations to public databases such as ClinVar, we’re not only helping individual patients, but we’re also advancing collective knowledge and reducing uncertainty across the field. 

Q6: How does rare disease diagnostics connect to drug development and clinical research? 

Dr. Bob Daber: 

There are many symbioses across the healthcare system that advance drug discovery. What differentiates our contribution is not just the size of the dataset but the depth and quality of the interpretation behind it. Because our data is built on rigorously curated variant classifications and longitudinal clinical insights, it can be used with confidence to support therapeutic discovery, refine trial eligibility criteria, and identify patient populations with greater precision.  

In rare disease, where each data point carries outsized importance, this level of interpretation accelerates discovery and brings therapies closer to the patients who need them most. 

Q7: Looking ahead, what gives you optimism about the future of rare disease diagnosis? 

Dr. Bob Daber: 

We’re moving toward a future in which earlier, more precise genetic insights are part of routine care—especially in settings like the NICU, where rapid diagnosis can dramatically change outcomes. As datasets grow and interpretation frameworks evolve, fewer variants will remain unresolved. 

Every variant we resolve represents progress for patients and families who have waited years for answers, and that progress can be life-changing. 

To read Dr. Bob Daber’s whole perspective on how variant interpretation at scale is transforming rare disease diagnosis, read the full STAT article here.