an asterisk (*) character followed by a number. The most common variant (also called wild type) has CYP2C19*1 label. The variant genotypes of CYP2C19*2 (NM_000769.2:c.681GA; p.Pro227Pro; rs4244285), CYP2C19*3 (NM_000769.2:c.636G>A; p.Trp212Ter; rs4986893) and CYP2C19*17 (NM_000769.2:c.-806C>T; rs12248560) are major factors attributed to interindividual differences in the pharmacokinetics and response to CYP2C19 substrates. CYP2C19*2 and *3 (loss-of-function alleles) are associated with diminished enzyme activity, whereas CYP2C19*17 (gain-of-function allele) results in increased activity. The Working Group of the Association for Molecular Pathology Clinical Practice Committee recommended these three variant alleles to be included in the minimal clinical pharmacogenomic testing panel, called tier 1. The extended panel of variant alleles, called tier 2, additionally includes the following CYP2C19 alleles: *4.001 (*4A), *4.002 (*4B), *5, *6, *7, *8, *9, *10, and *35, all of them associated with diminished enzyme activity. Although these tier 2 alleles are included in many platforms, they were not included in the tier 1 recommendations because of low minor allele frequency (which can increase false-positive occurrences), less well-characterized impact on CYP2C19 function, or a lack of reference materials. In partnership with the clinical testing community, the Centers for Disease Control and Prevention established the Genetic Testing Reference Material Program to meet the need for publicly available characterized reference materials. Its goal is to improve the supply of publicly available and well-characterized genomic DNA used as reference materials for proficiency testing, quality control, test development/validation, and research studies. The allele frequencies of CYP2C19*2 and *3 are significantly higher in Chinese populations than in European or African populations, and are found at approximately 3–5% of European and 15–20% of Asian populations. Among Arab population, the frequency of CYP2C19 genotypes including *1/*17, *1/*2, *2/*2, *3/*3, and *1/*3 were 20.2%, 16.7%, 6.1%, 5.45%, 0.7%, and 0.35%, respectively. In a study of 2.29 million direct-to-consumer genetics research participants, the overall frequencies of *2, *3, and *17 were 15.2%, 0.3%, and 20.4%, respectively, but varied by ethnicity. The most common variant diplotypes were *1/*17 at 26% and *1/*2 at 19.4%. The less common *2/*17, *17/*17 and *2/*2 genotypes occurred at 6.0%, 4.4%, and 2.5%, respectively. Overall, 58.3% of participants had at least one increased-function or no-function CYP2C19 allele. CYP2C19 is involved in processing or metabolizing at least 10% of commonly prescribed drugs. Variations to the enzyme can have a wide range of impacts to drug metabolism. In patients with an abnormal CYP2C19 variant certain benzodiazepines should be avoided,