We have expanded our diagnostics portfolio and now offer whole genome diagnostics as an additional option for rare, unsolved cases. The new service serves as a second-tier test for patients who remain undiagnosed even after high-quality exome diagnostics such as our ExomeXtra®.
Trio ExomeXtra® Remains the Most Effective Approach to Clarify Genetic Diseases
ExomeXtra® is our first-line diagnostic test for patients with suspected genetic disorders. Its customized design provides deep, uniform coverage of almost all disease-relevant regions, enabling high sensitivity and clinically meaningful findings. Especially when performed as a trio analysis, it provides clear diagnoses: multiple cohorts show a 5–15 percentage-point increase in diagnostic yield when parental data are included. Inheritance information greatly improves variant interpretation, particularly in complex or nonspecific phenotypes1,2,3. In contrast, switching from exome to genome diagnostics typically results in only a 1–5 percentage-point increase in diagnostic yield4.
This is also because, contrary to what is assumed, the broader coverage of whole genome diagnostics rarely contributes to greater diagnostic clarity. Most additional findings fall into the category of variants of uncertain significance. At the same time, whole genome diagnostics reduces sensitivity by trading depth for breadth, which is a disadvantage in clinically relevant regions. For most diagnostic scenarios, high-quality, customized exome diagnostics such as our Trio ExomeXtra® remains the more effective first step.
Whole Genome Diagnostics Solves Cases of Structural Variants
Despite the considerable advantages of ExomeXtra®, a small number of patients remain without a genetic explanation. In some of these cases, the cause may be a structural or complex variant, or a deep intronic change that cannot be fully resolved with exome-based diagnostics. For such cases, whole genome diagnostics can deliver the missing information by covering the entire genome and enabling the detection of inversions, translocations, insertions and other large or complex rearrangements.
With our new Whole Genome Diagnostics, we close this gap in our exome diagnostics. By combining Trio ExomeXtra® with this new service as a focused second-tier option, we remain true to our mission – always offering the best approach to diagnosing rare diseases. We draw on our years of experience in genetic diagnostics and apply the same quality principles and expert insights that underpin our exome enrichment workflow, to ensure that our Whole Genome Diagnostics truly meets our high diagnostic standards. If you would like to discuss whether our Whole Genome Diagnostics is appropriate for a specific case, our team will be happy to advise you.
- Malmgren, H. et al. Diagnostic yield of 1000 trio analyses with exome and genome sequencing in a clinical setting. Frontiers in genetics. 16:1580879. doi: 10.3389/fgene.2025.1580879. (2025)
- Farwell, K. D. et al. Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. Genetics in medicine. 17(7):578-86. doi: 10.1038/gim.2014.154. (2015)
- Retterer, K. et al. Clinical application of whole-exome sequencing across clinical indications. Genetics in medicine. 18(7):696-704. doi: 10.1038/gim.2015.148.(2016)
- Battke, F., Schulze, M., & Schulte, B. What Is the Real Diagnostic Benefit of Whole-Genome Sequencing?. Preprints. https://doi.org/10.20944/preprints202412.0023.v1 (2024)