Genotype-Phenotype Mapping for Guideline and Drug Label Curation

ClinPGx now uses CPIC/ClinPGx allele function and phenotype mappings and terms for guideline and drug label curation, including the interactive genotype picker tools on DPWG guideline annotation pages. If a DPWG guideline gene is not a CPIC gene, then we will continue to use DPWG mappings based on documents previously downloaded from the KNMP website. The DPWG terms and mapping largely agree with CPIC/ClinPGx across genes, but exceptions are noted on the DPWG mappings page. We will also continue to use CPIC/ClinPGx mappings for FDA label curation and FDA Table of Pharmacogenetic Associations entries. The FDA does not provide genotype-to-phenotype mapping information to our knowledge.

Previously, we attempted to use DPWG mappings for DPWG guideline annotations. We received feedback that this caused confusion when using PharmDOG and GSI when the CPIC/ClinPGx and DPWG assignments differed. In these cases, two different metabolizer statuses were shown for the same diplotype - one phenotype was used to retrieve CPIC and FDA guidance while another was used to retrieve the DPWG guideline recommendation. Another source of confusion was that the alleles listed in the DPWG documents and guideline publications are often a smaller set than what is available on PharmVar, resulting in a number of diplotypes with a CPIC phenotype assignment and guidance but without a DPWG phenotype assignment and guidance. Additionally, the gene documentation on the KNMP website moves over time and our team is not always able to find the same source documents as these website changes occur; updates are not readily apparent and might only be in found in the DPWG guideline publications and supplements. Due to these issues, we will use CPIC/ClinPGx assignments for genotype-phenotype translation going forward for all guideline annotations.