In 2016, CPIC led a consensus effort to standardize terms for clinical pharmacogenetic tests. The goal of the project was to create standardized terms for pharmacogenetic allele function and phenotypes to be used in CPIC guidelines (specifically Tables 1 and 2) and in the larger pharmacogenetics community (Term Standardization Part 1). However, additional standardization opportunities exist beyond the genes included in this project. For example, VKORC1 is a CPIC level A gene (https://cpicpgx.org/genes-drugs) on which we did not reach a consensus. This gene is tested primarily in the context of predicting starting doses of the common anticoagulant warfarin, which is also dependent on CYP2C9. Therefore, many laboratories report a drug-centered phenotype such as “greatly increased sensitivity to warfarin” (see the CPIC guideline for warfarin), which complicated standardization of VKORC1 terms following the formats used for other genes. Other genes such as RYR1, CACNA1S, CFTR, G6PD, IFNL3, and mtRNR1 (guideline in progress) have CPIC guidelines but standardized terms describing allele function and phenotype do not exist. In addition to these genes with CPIC guidelines, there are also genes without CPIC guidelines but are CPIC level A, B, or C genes that may need to be considered in the future such as GBA, NAGS, HPRT1, POLG, COMT, OPRM1, SCN1A, SLC6A4, F5 and urea cycle enzymes (ABL2, ASL, ASS1, CPS1, and OTC).
CPIC has initiated a second term standardization project that will cover allele and phenotype terms for these additional genes. The purpose of this project is to standardize additional terms that are used to characterize pharmacogenetic allele functional status and the presumed phenotype (generally based on diplotypes), and to encourage adoption by external groups (e.g., ClinGen, SNOMED, EHR vendors, clinical laboratories etc.).
MT-RNR1 consensus terms-Public comment period deadline May 28th, 2021. Send feedback to firstname.lastname@example.org.