Oncology

Session # P-051

Application of deep mutational scanning data for MLH1 variant interpretation

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. 

  1. 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. 

  1. Overall demonstrated a successful validation of saturation scale functional testing via DMS to provide evidence for improved 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
  • Collaborators: University of Michigan
  • Conference: CGA-IGC 2023
  • Date: Thursday, Oct 26, 2023 8:00am - 1:30pm

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