Variant Effects Program

Genome sequencing has revolutionized biomedical research and clinical diagnostics, but there is a critical gap, Most genetic variants remain functionally uncharacterized. These "variants of uncertain significance" (VUS) leave patients without answers, slow drug development, and impede progress in precision medicine.

The Variant Effects Program at BBI and the Department of Genome Sciences at the University of Washington has pioneered a technology-first, systematic approach to closing this gap and revealing variant function. We’ve led the development of Multiplexed Assays of Variant Effect (MAVEs), technologies to analyze, measure and model the functional consequences of genetic variants at scale. We have also led the clinical translation of the data we produce, reshaping how genetic variants are interpreted.

More Resources:

How does our technology work? Here is an introduction to Deep Mutational Scanning

Case Study: Understanding haemophilia, one amino acid at a time

We’d love to explore a partnership focused on your top-priority genes, reach out to us at info@brotmanbaty.org for more information.

Our Variant Effects Program is a unified platform that equips researchers, clinicians, and patients with clear, actionable insights into the complexities of genetic variation.

Current initiatives include:

NIH funded

• Center for the Multiplex Assessment of Phenotype (CMAP):Center for the Multiplex Assessment of Phenotype (CMAP): A Center of Excellence in Genome Science.
• Center for Actionable Variant Analysis (CAVA): Part of the Impact of Genetic Variation on Function
• Expanding Clinical Use of Variant Data: Translating complex data into practical applications for healthcare providers and their patients.
  
  

CZI funded

• Rare Variant Exploration: Unlocking insights into rare genetic variants that shape individual health outcomes.

We're also helping to democratize the methodology, provide training, define and set standards through global collaboration through the Atlas of Variant Effects (AVE) Alliance.

Resources:
BBI-CVD: hub connecting researchers studying rare disease genetics with clinicians applying precision genomics to care for patients with rare diseases
MaveDB: open-source, public repository for datasets from Multiplexed Assays of Variant Effect (MAVEs)

Further Information

• DNA Today Podcast - Revolutionizing Variant Curation with MAVEs
• GA4GH Podcast - interpreting human genetic variation
• Variants and Us (VUS) Podcast
• Introduction to Deep Mutational Scanning (Animation)
• Researchers, Clinicians, Funders Create Roadmap for Clinical Atlas of Variant
• An Atlas of Variant Effects to understand the genome at nucleotide resolution