For patients with a suspected rare disease, the path to a diagnosis can feel endless after years of appointments, inconclusive tests, and unanswered questions. Today, advances in genetic testing, such as exome and genome sequencing, are helping to shorten that journey. Since roughly 80% of rare diseases have a genetic cause¹, genetic testing can be powerful in uncovering answers that were previously out of reach.
However, the technology alone is not enough. The clinical context, including the patient’s symptoms, history, and overall presentation, is just as important. In this blog, we explore how genomic data and clinical insights work together to help provide clearer answers for patients and families.
Historically, genetic testing has often started with targeted gene panels, which look at a specific set of genes based on a suspected diagnosis. For example, a child with signs of a neuromuscular condition might receive a panel focused on a few hundred genes known to be associated with those disorders.
This approach makes sense in theory, but in practice it has limitations. Many rare diseases share overlapping symptoms, and the true cause may lie outside of the genes included in a given panel. When results come back negative, clinicians often continue the clinical guesswork— ordering another panel, and then another. For families, this can mean a long and frustrating cycle without clear answers.
Whole-genome sequencing (WGS) takes a different approach. Instead of testing only a pre-selected group of genes, it analyzes nearly all of a patient’s genetic code at once.
This creates a much more comprehensive view of potential disease-causing changes and removes the need to guess in advance which genes might be involved. For patients with suspected genetic conditions, especially children, this more comprehensive approach can significantly improve the chances of finding a diagnosis earlier in the diagnostic journey.2,3
Making Sense of the Data: Why Clinical Phenotyping Matters
This is why clinical phenotyping is so important. Understanding the detailed clinical picture of a patient’s condition—symptoms, physical features, developmental history, test results, and how the condition has changed over time— helps prioritize genetic variants that are most likely to explain the patient’s symptoms.
Phenotype-driven analysis can be revisited and reinterpreted over time as new clinical information emerges, whereas traditional gene panels test a fixed set of genes and offer little room for reinterpretation.
This becomes especially important when a result is uncertain. In many cases, genetic testing identifies a variant of uncertain significance (VUS)—a change in DNA where it is not yet clear whether it is harmful. In these situations, the clinical context is essential. A variant in a gene that closely matches a patient’s symptoms may be much more meaningful than the same variant found in a completely unrelated clinical picture. Clinical phenotyping helps prioritize which findings to investigate further.
Moreover, the clinical picture doesn’t end when a test is ordered. Patients evolve over time, and new symptoms or findings can change how genetic data is interpreted. Updated clinical information can refine the analysis and, in some cases, lead to a diagnosis that wasn’t apparent earlier.
How MyOme Combines Genomic and Clinical Insights to Enable Diagnosis
At MyOme, clinical phenotyping is more than a checkbox — it's ingrained into our diagnostic process.
All clinical information provided is directly integrated into our analysis pipeline to guide which genetic variants are prioritized. If the initial analysis doesn't yield a diagnosis, the phenotypic context is used to expand the search and explore new ways to uncover diagnoses — such as performing methylation analysis and long-read sequencing — all within the same workflow.
The bottom line: the clinician’s understanding of the patient and the power of our genomic technology work best together. The more complete the clinical information, the more likely we are to find a meaningful answer.