Jakob Jespersen, member of Lage Lab at MGH and the Broad Institute, presented at the Center for Mendelian Genetics Analysis meeting the Interpretation of missense variants using protein structures and features. Jakob explained that with a vast amount of exome sequencing data, it is difficult to identify the missense variants that may be implicated in diseases. While it is possible to crudely classify variants as “loss of function” based on observations such as the mutation being in a splice site, creating a stop codon or frameshift, it is much more difficult to determine whether missense mutations are deleterious or benign.
Since the Protein Data Bank (PDB) hosts information on more than 6,000 different human proteins, it is possible to add structural information to help the classification of missense mutations. Some methods are already utilizing features from 3D protein structures, so the presentation was focused on features that we can extract and calculate which are not in use yet as well as a computational tool set Jakob has developed for this purpose.
Enjoy the recording of the Jakob’s presentation in the video below (Sep 20th, 2016)