A taxonomic schema of potential pitfalls in clinical variant analysis based on real-world evidence.

Abstract

The classification and interpretation of genetic variants associated with genetic diseases have been shown to vary between clinical genetic laboratories. This can lead to errors introduced in the interpretation and public presentation of genetic findings in the literature and available databases. This qualitative study utilizes real-world evidence to introduce a taxonomic schema of potential pitfalls associated with public and commercial resources commonly used for sequence variant analysis. Databases, articles and other resources continue to evolve over time. A modified and expanded version of Reason's Model of Human Error with respect to variant analysis is proposed and discussed. This study complements professional standards and published recommendations of interpretive considerations associated with variant analysis and expands the scope of professional competency.