CYP2C19*2 core allele definition update

PharmVar released changes and additions to the CYP2C19 allele definitions which includes an update of the CYP2C19*2 core allele definition.

Prior to the latest release, the CYP2C19*2 allele was defined by three core variants, c.332-23A>G (splice defect), c.681G>A (splice defect) and c.991A>G (p.I331V, which is present in most CYP2C19 alleles including CYP2C19*1).

The publication "CYP2C19 c.681G>A Is not in Complete Linkage Disequilibrium With c.332-23A>G: Implications for Pharmacogenetic Testing" by Turner et al. (PMID: 42535320) reports the discovery of new CYP2C19*2 sequences that lack c.332-23A>G (CYP2C19*2.018 and CYP2C19*2.019) and one that lacks c.991A>G (CYP2C19*2.019). Consequently, the CYP2C19*2 core allele definition was updated based on the PharmVar Designation Criteria and c.681G>A is now the only core variant defining this allele.

Most ClinPGx star allele definitions are based on PharmVar core alleles. To stay aligned among the pharmacogenomic resources, ClinPGx updated the CYP2C19 allele definitions based on the PharmVar release.

To reflect the overlap in variation among the CYP2C19 alleles, described in part in Turner et al. (PMID: 42535320) and visible in the PharmVar's Cave Compare View, ClinPGx relies on the use of UPAC nucleotide codes. The CYP2C19*2 definition on ClinPGx is represented as c.332-23R, c.449R, c.681A, and c.991R, which uses the ambiguous nucleotide code "R" to reflect that position c.332-23, c.449, and c.991 can be either a "G" or an "A" in the CYP2C19*2 core allele. For more information, see the CYP2C19*2 page and on the Notes tab of the CYP2C19 Allele Definition Table.