^*Level of evidence [42]: Level 1A, annotation for a variant-drug combination in a CPIC or medical society-endorsed pharmacogenomic guideline, or implemented at a PGRN site or in another major health system. Level 1B, annotation for a variant-drug combination where the preponderance of evidence shows an association. The association must be replicated in more than one cohort with significant P values and preferably will have a strong effect size. Level 2A, annotation for a variant-drug combination that qualifies for level 2B where the variant is within a very important pharmacogene as defined by PharmGKB. The variants in level 2A are in known pharmacogenes; therefore, functional significance is more likely. Level 2B, annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but some studies may not show statistical significance, and/or the effect size may be small. Level 3, annotation for a variant-drug combination based on a single significant (not yet replicated) annotation for a variant-drug combination evaluated in multiple studies but lacking clear evidence of an association. Level 4, annotation based on a case report, non-significant study, or in vitro, molecular, or functional assay evidence only (https://www.pharmgkb.org/).

Abbreviations: LOE, level of evidence; ADR, adverse drug reaction; NACB, National Academy of Clinical Biochemistry [19]; CLSI, Clinical and Laboratory Standards Institute, MM19AE [18]; Clinical chemistry textbook, Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th ed. Elsevier [37]; CPIC, Clinical Pharmacogenetics Implementation Consortium [383940]; DPWG, Dutch Pharmacogenetics Working Group [41].