Fig. 1: Classification of clinically relevant variants in 2628 Rotterdam Study participants in the 59 American College of Medical Genetics and Genomics–Association for Molecular Pathology (ACMG-AMP) genes according to ClinVar version 2018 and the Human Gene Mutation Database (HGMD).

Classes are defined per the ACMG-AMP guidelines: (1) benign, (2) likely benign, (3) uncertain, (4) likely pathogenic, (5) pathogenic. Variants absent from the database are coded as 0. The classifications for HGMD were converted to class 3 (No interpretation available (NA), functional polymorphism (FP) and disease polymorphism (DP)), class 4 (disease functional polymorphism (DFP), possible disease mutations (DM?)) and class 5 (disease mutation (DM). For visualization purposes, the variants observed in autosomal recessive genes ATP7B and MUTYH are not shown. The numbers at the sides are sums for that respective classification.