to metabolite – is higher in PMs. A study of the ability to metabolize warfarin among the carriers of the most well-characterized CYP2C9 genotypes (*1, *2 and *3), expressed as percentage of the mean dose in patients with wild-type alleles (*1/*1), concluded that the mean warfarin maintenance dose was 92% in *1/*2, 74% in *1/*3, 63% in *2/*3, 61% in *2/*2 and 34% in 3/*3. CYP2C9*3 reflects an Ile359-Leu (I359L) change in the amino acid sequence, and also has reduced catalytic activity compared with the wild type (CYP2C9*1) for substrates other than warfarin. Its prevalence varies with race as: Test panels of variant alleles The Association for Molecular Pathology Pharmacogenomics (PGx) Working Group in 2019 has recommended a minimum panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) to be included in assays for CYP2C9 testing. CYP2C9 variant alleles recommended as Tier 1 by the PGx Working Group include CYP2C9 *2, *3, *5, *6, *8, and *11. This recommendation was based on their well-established functional effects on CYP2C9 activity and drug response availability of reference materials, and their appreciable allele frequencies in major ethnic groups. The following CYP2C9 alleles are recommended for inclusion in tier 2: CYP2C9*12, *13, and *15. CYP2C9*13 is defined by a missense variant in exon 2 (NM_000771.3:c.269T>C, p. Leu90Pro, rs72558187). CYP2C9*13 prevalence is approximately 1% in the Asian population, but in Caucasians this variant prevalence is almost zero. This variant is caused by a T269C mutation in the CYP2C9 gene which in turn results in the substitution of leucine at position-90 with proline (L90P) at the product enzyme protein. This residue is near the access point for substrates and the L90P mutation causes lower affinity and hence slower metabolism of several drugs that are metabolized CYP2C9 by such as diclofenac and flurbiprofen. However, this variant is not included in the tier 1 recommendations of the PGx Working Group because of its very low multiethnic minor allele frequency and a lack of currently available reference materials. As of 2020, the evidence level for CYP2C9*13 in the PharmVar database is limited, comparing to the tier 1 alleles, for which the evidence level is definitive. Additional variants Not all clinically significant genetic variant alleles have been registered by PharmVar. For example, in a 2017 study, the variant rs2860905 showed stronger association with warfarin sensitivity (<4 mg/day) than common variants CYP2C9*2 and CYP2C9*3. Allele