Presented at ACMG 2025 by Genomenon’s Founder and Chief Scientific Officer, Mark Kiel, MD, PhD.
Leveraging real-world evidence (RWE) from the literature, we developed a comprehensive database of disease-causing GLA variants that details their roles in disrupting enzyme function and driving clinical disease.
Notably, our establishment of a novel GLA (a-Gal A) enzyme activity threshold led to the reclassification of over 56% of previously ambiguous variants (VUS) to pathogenic—an adjustment projected to impact the diagnostic categorization of a significant number of Fabry patients.
This achievement exemplifies the transformative power of real-world evidence in refining diagnostic criteria and enhancing our understanding of disease pathobiology. Together with the clinically reported variants from ClinVar, our resource stands to significantly improve the diagnosis and treatment of Fabry disease within the medical community.
