In the fast-moving world of genetic testing, designing and updating a hereditary cancer portfolio and each test it includes is a balancing act. It’s about making sure we include genes that matter clinically while steering clear of those with uncertain links to cancer. At Ambry, we’ve perfected this balancing act by sticking to a process rooted in solid science and clinical utility, giving health care providers the information they need to manage their patients confidently.

Defining the Test

The first step in designing a hereditary cancer multigene test at Ambry involves defining the scope of the test. This definition includes determining whether the panel will be disease-specific or multi-disease-specific, tailored to the different needs of various patient populations and clinical scenarios. The decision is guided by the latest literature, research and understanding of disease states.

Assessing Evidence Levels

Once the test definition is set, we evaluate the evidence for each gene’s inclusion. Our goal is to determine if a gene has clear clinical guidance—meaning healthcare providers can act on the results—or if it lacks strong evidence, making its clinical impact less certain. We focus on genes with strong evidence and clinical utility, ensuring that our tests will provide genetic information that makes a real difference for patients and their families.

Gene-Disease Validity Framework

At Ambry, we use a rigorous gene-disease validity (GDV) framework, part of our Classifi™ program, to assess whether a gene truly belongs on the panel. Our team of experts constantly reviews the latest data to ensure that the genes included are strongly associated with cancer risk. This commitment to keeping our panels up-to-date helps ensure they remain clinically relevant and scientifically accurate.

Adding and Removing Genes

Deciding whether to add, keep or remove genes from a panel is a dynamic, ongoing process. We’re always reviewing the latest scientific evidence and clinical guidelines. When it comes to adding genes, we focus on those that have strong gene-disease validity and clear clinical utility. Alternatively, if a gene shows limited clinical utility or a weaker link to the disease, we remove it. This helps reduce the number of variants of uncertain significance (VUS), as genes with limited evidence tend to produce only VUSs, which we know can be confusing for both patients and health care providers.

Innovative Options for Genes With Limited Evidence

In the context of hereditary cancer testing, limited evidence genes are genes that are not clearly associated with cancer predisposition. When a gene’s association with cancer is unclear, a variant detected in that gene cannot be classified as pathogenic (harmful), even if the variant might affect how the gene functions. Put simply, a variant in that gene cannot be classified as pathogenic.

Ambry carefully curates each test to be clinically actionable, but we know genetic testing isn’t one-size-fits-all, so we offer a unique solution: optional add-ons. These allow health care providers to decide if they want to include limited evidence genes based on their patient’s specific case. It’s another way we ensure our guideline-based tests and base panels remain focused on the most clinically impactful genes while offering flexibility for personalized care.

Continuous Improvement

The truth is, in genetic testing, bigger panels aren’t always better. As our understanding of genetics grows, so does our approach to refining these panels. At Ambry, we continuously update our tests based on the latest research, ensuring they deliver the most accurate and actionable information. This ongoing improvement helps lead to better patient outcomes.

Designing hereditary cancer tests is all about finding the right balance, and we’ve developed a process that does just that. From clearly defining each test based on clinical indication to assessing the evidence and making thoughtful decisions on which genes to include or remove, we prioritize clinical utility. Offering optional add-ons for genes with limited evidence gives health care providers the flexibility they need to tailor testing for their patients. This balanced approach ensures that our panels remain relevant and impactful, helping clinicians manage hereditary cancer risk with confidence.

Jessica Grzybowski, MS, CGC

After completing her Bachelor of Science in biology from the University of Wisconsin, Jessie Grzybowski, MS, CGC, earned her Master of Science in genetic counseling from Northwestern University in 2008. Before joining Ambry in 2014, Grzybowskiworked as a clinical cancer genetic counselor at various community-based hospitals and academic medical centers in both Chicago and Southeastern Wisconsin. As Ambry’s associate director of the clinical strategy team, Grzybowski oversees strategic initiatives and continues to collaborate closely with key opinion leaders in the oncology field, providing scientific and clinical expertise to support the development and commercialization of products and services.