Expanding the knowledge base for TK2D beyond what was available in ClinVar and other public resources.
Nearly one quarter of these were pathogenic or likely pathogenic, significantly strengthening the evidence base for diagnosis to drive increased patient identification.
A previously uncertain variant was reclassified as likely pathogenic, enabling faster and more accurate diagnosis.
Evidence made freely available in ClinVar and Mastermind ensures global visibility and consistent use across labs.
TK2D is an ultra-rare, progressive mitochondrial myopathy characterized by proximal muscle weakness and severe respiratory involvement. Respiratory failure is a leading cause of mortality, especially with early onset. Overlapping symptoms with better-known neuromuscular diseases and frequent variants of uncertain significance (VUS) on genetic tests prolong the diagnostic odyssey. Because of its rarity and genetic complexity, TK2D remains underrecognized and underdiagnosed, with many clinically observed variants missing or underrepresented in ClinVar.
UCB set out to raise disease awareness and shorten time-to-diagnosis by ensuring that every literature-supported TK2 variant and its evidence could be found, trusted, and used by the global community.
Extract literature-driven real-world evidence: Genomenon used AI-powered search and expert review to scan the biomedical literature and curate TK2 variants according to ACMG/AMP guidelines.
Build the TK2 variant knowledgebase: 95 variants were curated, 40 percent of which were absent from ClinVar, including 25 percent that were pathogenic or likely pathogenic. A previously uncertain variant was reclassified as likely pathogenic.
Share the results with the world: Variants and supporting evidence were made freely available in Genomenon’s Mastermind Genomic Intelligence Platform to maximize reach and utility.
Maintain a living knowledgebase: Annual updates ensure new findings and reclassifications are incorporated and shared with the global community.
“People living with TK2D and their families face extraordinary challenges due to the rarity and complexity of this disease. By partnering with Genomenon, we are helping to close critical knowledge gaps, accelerate accurate diagnosis, and support the global research community in their efforts to bring hope and new possibilities to those affected by TK2D. Making curated variant data accessible to all is a vital step toward improving patient outcomes and advancing the field of rare disease research.”
Sarah Chang, Ph.D., Medical Strategy Lead, UCB
Improved diagnostic confidence: Reclassification of VUS to likely pathogenic accelerates diagnosis.
Global knowledge sharing: Evidence is distributed openly to clinicians and researchers worldwide.
Consistent lab interpretation: A robust, standardized knowledgebase reduces variability in testing.
Sustained awareness: Annual updates ensure TK2D variant data remains current and actionable.
Genetic Disease Sponsorship enables biopharma partners to promote awareness and increase diagnostic rates by underwriting the creation, curation, and public distribution of a comprehensive, literature-driven variant knowledgebase, kept current over time and made accessible to clinicians and researchers globally.
We help provide insights into key genetic drivers of diseases and relevant biomarkers. By working together to understand this data, we enable scientists and researchers to make more informed decisions on programs of interest. To learn more about how we can partner together to find your genomic variant solutions, we invite you to click on the link below.
