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. 

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.