Clinical Variant Analysis

The clinical interpretation of variants in Next-Gen Sequencing is a quickly evolving field. While the body of knowledge is growing exponentially, experts have to derive sound, clinical decisions leveraging an ever-expanding set of specialty databases, clinical publications, and algorithms that are designed to predict the impact of specific variants in the resulting protein.

The specific steps and considerations that need to be considered are defined by the American College of Medical Genetics and Genomics. The guidelines for the interpretation of sequenced variants were published in 2015 with an addendum for loss of function variants added in 2018. A second set of guidelines for interpreting Copy Number Variants (CNVs) was published in 2020.

In this eBook, I have summarized the key concepts of these guidelines, including:

• What defines a pathogenic and respectively a benign variant
• Scoring mechanisms that allow us to classify a variant clinically
• A few interesting cases of variants and their classifications

This eBook is designed to show how we are able to support this equally complex and tedious process with our clinical interpretation solution VSClinical.