Session # PB1030

Application of deep mutational scanning data for MLH1 variant interpretation

Presenting Author: Anthony Scott (University of Michigan)

Take home points: 

1. Investigators found high correlation between DMS functional scoring and clinical classifications wherein variants with abnormal DMS-function were typically classified as pathogenic and normal DMS-function were classified as benign.
2. Improved Lynch Syndrome Interpretation: Integrating DMS data into clinical databases enabled precise assessment of MLH1 missense variants. DMS-guided reclassification for uncertain variants improves genetic testing accuracy and clinical decision-making.
3. Overall demonstrated a successful validation of saturation scale functional testing via DMS to provide evidence for improved MLH1 variant interpretation.

• Title: Application of deep mutational scanning data for MLH1 variant interpretation
• Authors: Anthony Scott; Xiaoyan Jia; Grace Clark; Sajini Jayakody; Bala Burugula; Jacob Kitzman; Felicia Hernandez; Rachid Karam; Ashley P.L. Marsh; Sami Belhadj; Matthew Varga
• Conference: ASHG 2023
• Date: Thursday, Nov 02, 2023 3:00pm - 5:00pm