Abstract 14451: High Agreement Between a Cardiology Specific Scoring System and the ACMG Criteria for Genetic Variant Interpretation and Classification

Introduction: The assessment of pathogenicity of genetic sequence variants is probabilistic and remains a challenge. Recently a consensus recommendation for genetic variant interpretation and classification has been published by the American college of medical genetics (ACMG). We evaluated the agreement between these recommendations and a previously published scoring system that was developed specifically for cardiomyopathies and primary electrical diseases by the Amsterdam group (Amsterdam criteria = AC). Methods: We included rare genetic variants (prevalence <0.1% in ExAC) that were identified in the first 524 probands who were sequenced using a cardiology specific gene panel (75 genes) at our institution. These variants were classified by both the AC and ACMG criteria using a 5-tier-classification system: class 1 (benign), class 2 (likely benign), class 3 (variant of unknown significance), class 4 (likely pathogenic) or class 5 (pathogenic). The agreement between the two classification systems was eval...