The current state of clinical interpretation of sequence variants

Abstract

Accurate and consistent variant classification is required for Precision Medicine. But clinical variant classification remains in its infancy. While recent guidelines put forth jointly by the American College of Medical Genetics and Genomics (ACMG) and Association of Molecular Pathology (AMP) for the classification of Mendelian variants has advanced the field, the degree of subjectivity allowed by these guidelines can still lead to inconsistent classification across clinical molecular genetic laboratories. In addition, there are currently no such guidelines for somatic cancer variants, only published institutional practices. Additional variant classification guidelines, including disease- or gene-specific criteria, along with inter-laboratory data sharing is critical for accurate and consistent variant interpretation.