Tina Pesaran: 'By backing community initiatives like the AVE Alliance, we help establish the standardized, ancestry-agnostic frameworks necessary to reduce VUS rates and improve outcomes for all patients.'
[Editor’s Note: Ambry Genetics is a gold sponsor of the 2026 Mutational Scanning Symposium this week in Melbourne, Australia. Here, the company’s Vice President for Genome Science, Tina Pesaran, MA, MS, CGC, shares observations and insights into reasons behind that sponsorship and efforts to address genetic variants of unknown significance.]
Why has Ambry chosen to sponsor the 2026 Mutational Scanning Symposium and how does it align with the company’s mission?
Ambry has chosen to sponsor the 2026 Mutational Scanning Symposium to support the broader scientific community in scaling the generation and application of functional data. Advancing this field requires close collaboration between the experimentalists creating Multiplexed Assays of Variant Effect (MAVEs) and the clinical laboratories translating them into patient care. By backing community initiatives like the AVE Alliance, we help establish the standardized, ancestry-agnostic frameworks necessary to reduce VUS rates and improve outcomes for all patients.
What does Ambry hope to achieve at the symposium? Define “success.”
Ambry aims to use this symposium to discuss the critical steps needed to translate MAVE outputs and functional scores into clinically meaningful evidence for variant classification. Success for Ambry is defined by fostering seamless, real-world collaboration between the researchers who conduct these functional assays and the clinical laboratories that maintain robust variant databases and perform the variant classification. Ultimately, Ambry’s overarching measure of success is the widespread integration of MAVE evidence to reduce the rate of Variants of Uncertain Significance (VUS), advance precision medicine, and dramatically improve clinical decision-making and outcomes for patients.
How does mutational scanning factor into Ambry’s work in variant interpretation and genetic testing?
Mutational scanning is foundational to how Ambry resolves ambiguous genetic test results. Through our Classifi® program, we have actively translated MAVE data since 2019 to classify variants across genes like BRCA1, BRCA2, MUTYH, VHL, MSH2, RAD51C, and BAP1. This high-throughput approach evaluates thousands of variants simultaneously, providing ancestry-agnostic evidence that helps reduce racial disparities in classification. It also allows us to proactively assess novel variants before they are observed in patients, lowering initial VUS rates. To date, this effort has upgraded hundreds of VUS, downgraded thousands, and reduced diagnostic uncertainty for tens of thousands of patients.
As a member of the ClinGen/AVE Functional Data Working Group, Tina, what do you see as the most compelling near-term application of Multiplex Assays of Variant Effect (MAVE) data in a clinical or diagnostic context?
The most exciting near-term goal is integrating MAVE-derived evidence into the ACMG/AMP framework alongside other clinical data. By calibrating these at-scale assays against known “truth sets,” we can help Variant Curation Expert Panels (VCEPs) resolve VUS much faster than traditional methods allow.
