Monday, July 6, 2020

PharmVar GeneFocus paper for CYP2C19 is published

The PharmVar GeneFocus: CYP2C19 paper, the second of the GeneFocus series, has just been published by Clinical Pharmacology & Therapeutics.
PharmVar thanks all CYP2C19 experts as well as the PharmGKB team who have served on this panel and diligently curated this gene and reviewed submissions ever since PharmVar was launched back in 2017. This review provides a general overview of CYP2C19 as well as a deeper dive into the nomenclature.
The GeneFocus also provides a summary of a revision of CYP2C19*1. This revision was introduced to apply PharmVar allele definition criteria consistently across all CYP2C19 haplotypes, as well as to align definitions with the current reference sequence and its recently released LRG. Highlights of the revision include:
·       All but one *1 suballele contained g.80161A>G (I331V), which posed a conflict as this SNP is also present on many other star alleles 
·       To resolve this conflict, *1.001 (previously known as *1A) was revised to *38
o   This haplotype matches the NG_008384.3 RefSeq and LRG_584; therefore, there are no SNVs in the *38 core allele definition
o   All remaining *1 subvariants now contain g.80161A>G (I331V); consequently, g.80161A>G (I331V) has been added to the *1 core allele definition
·       *1 subvariants (with g.80161A>G (I331V)) are more commonly observed than *38
o   Commonly used genotyping platforms do not test for g.80161A>G (I331V) and thus, *1 will be assigned by default
·       The I331V amino acid change does not appear to impact function; therefore, both *1 and *38 are normal function
Changes such as the update from CYP2C19*1.001 to *38 may be viewed as ‘interruptive’. However, having standardized nomenclature that is consistently applied will greatly benefit the research and clinical PGx communities moving forward. The revision can now be found on the PharmVar page for CYP2C19.

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