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.

Thursday, June 11, 2020

LCD announces coverage for PGx testing under Medicare

The Centers for Medicare and Medicaid Services (CMS) have posted a FUTURE Local Coverage Determination (LCD) for MolDX: Pharmacogenomics Testing (L38294). This includes broad coverage for pharmacogenomic testing to go in effect this summer.

CPIC provided presentations to Palmetto prior to their draft LCD, and provided written comments on LCD ID L38294 back in November of 2019. CPIC members were instrumental in the feedback provided, and many of CPIC’s suggestions have been incorporated, and CPIC guidelines are cited throughout their document. For example, their post states:  “PGx tests are indicated when medications are being considered for use (or already being administered) that are medically necessary, appropriate, and approved for use in the patient’s condition and are known to have a gene(s)-drug interaction that has been demonstrated to be clinically actionable as defined by the FDA (PGx information required for safe drug administration) or Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines (category A and B).”

The LCD defines ‘actionable use’ of PGx as “when the genotype information may lead to selection of or avoidance of a specific therapy or modification of dosage of a therapy. The selection, avoidance, or dose change must be based on the FDA-label for the drug, an FDA warning or safety concern, or a CPIC level A or B gene-drug interaction”. PharmGKB uses the ‘Alternate Drug’ and ‘Dosing Info’ tags to highlight drug label annotations where the label contains information about contraindications or dosing changes based on genotype information. These tags can be used to filter our table of drug label annotations.

Monday, June 8, 2020

PGRN Transition

After 20 years of NIH funding, the Pharmacogenomics Research Network (PGRN) is becoming an independent scientific society on July 1, 2020. The deadline for becoming a founding member has been extended. If you are interested in joining, please visit

On behalf of all of the NIH PGRN funded investigators, we thank NIH for their past support, particularly our original program officer, Dr. Rochelle Long (NIGMS Director, Division of Pharmacology, Physiology and Biological Chemistry).

Update 6/29/2020 The inaugural Research In Progress (RIPS) webinar from the PGRN society will be given by Alan Shuldiner, MD, on Friday July 17 at 11am Eastern time. Dr. Shuldiner will speak on "Building bridges between industry, academia, health care systems and communities to advance Precision Medicine".

From Friday August 14, RIPS webinars will be held on the second Friday of every month at 11am Eastern time for all PGRN members. A schedule of upcoming RIPS webinars can be found here. If you are interested in joining the PGRN, you can become a member at

Friday, May 29, 2020

Dr. Stuart Scott joins Stanford

We are pleased to announce that Dr. Stuart Scott will be joining Stanford University as a Professor in the Department of Pathology effective 1 September 2020. In addition, Dr. Scott will be Laboratory Director of the Stanford Medicine Clinical Genomics Program. Dr. Scott is moving from the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai and Sema4 (previously the Mount Sinai Genetic Testing Laboratory). He is certified by the American Board of Medical Genetics and Genomics in both Clinical Molecular Genetics and Clinical Cytogenetics and Genomics. Dr. Scott’s research interests include pharmacogenomics (PGx), cytogenomics, epigenomics, and the implementation of genomic medicine. He has long standing collaborations with Stanford’s multi-institutional efforts in PGx including PharmGKB, CPIC, PharmVar and PharmCAT.

Tuesday, May 26, 2020

DPYD goes live on PharmVar

PharmVar has announced the introduction of DPYD to its database. DYPD is the rate limiting enzyme involved in the catabolism of fluoropyrimidines (5-fluorouracil and capecitabine) which are used in several cancer treatment regimens. Clinical laboratories provide preemptive DPYD genotyping to avoid potentially life-threatening toxicity in patients carrying DPYD risk alleles. Annotations of clinical guidelines for DPYD are available on PharmGKB here.

Prior to its introduction to PharmVar, there was no centralized resource for DPYD nomenclature. Some of the allelic variants were assigned star allele numbers when first published (DPYD*1-*13) or were referred to by a trivial name.

Although star nomenclature based on haplotypes was initially used to name DPYD variants, this system was deemed impractical for DPYD due to the size of the gene and recombination between exons. To accommodate DPYD (and other genes with similar challenges in the future), PharmVar has developed a gene page format using rsIDs as PharmVar names instead of star allele designations.

Check out the new DPYD page at PharmVar welcomes any feedback and encourages DPYD submissions to grow its inventory.

Monday, May 18, 2020

PharmGKB response to the FDA Table for Pharmacogenetic Associations

In February, the FDA posted the Table for Pharmacogenetic Associations (PGx Table), and PharmGKB and CPIC blogged about the table a few days later.  We identified substantial areas of overlap and some differences between the gene-drug pairs listed on the FDA table and those with published CPIC guidelines. It is important to note that the FDA PGx Table, CPIC, and PharmGKB may update their content at any time. These comments reflect the PGx table as of May 2020,

As of the current posting, the evidence the FDA used to construct the PGx Table is not explicitly posted, although most of the gene-drug pairs with therapeutic management recommendations on the PGx Table have labels also listed on FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling (Biomarker Table) containing some kind of prescribing information as defined by PharmGKB. The CPIC process for creating guidelines has been published and involves field experts conducting extensive reviews of the peer-reviewed literature, all of which is cited or listed as supporting evidence in the guideline publications.

Direct comparison of which gene-drug pairs have CPIC guidelines versus which are listed on the FDA PGx Table is difficult due to the completely different manners in which the pairs are selected and ranked, as well as the different content and purposes of CPIC and the FDA PGx Table. 

Here we present our compilation tables of the gene-drug pairs on FDA’s PGx table with CPIC gene-drug pairs (some of which have guidelines, some are pending, and some are not considered actionable), PharmGKB annotations of drug labels found on FDA’s Biomarker Table, PharmGKB clinical annotations, and PharmGKB annotations of clinical guidelines published by several groups, including CPIC.  These tables are updated manually and therefore may not be current with recent changes in clinical guidelines, the FDA Biomarker Table or PharmGKB clinical annotations at the time of download.

This blog post has also been submitted as a comment to the open docket at FDA.

Friday, May 1, 2020

Announcing Dr. Kelly Caudle as co-PI of CPIC

CPIC is pleased to announce that Dr. Kelly Caudle (St. Jude Children’s Research Hospital) joins Dr. Teri Klein (Stanford University) as the co-Principal Investigator of the NHGRI U24 grant (HG 010135) that provides funds for CPIC.

Dr. Caudle has been the CPIC Coordinator/Director for CPIC for 8 years. During this time she has overseen the CPIC guideline development for 22 CPIC guidelines and 13 guideline updates and has led several CPIC projects. We thank Dr. Mary Relling for her outstanding leadership and we are thrilled that she continue her involvement in CPIC as a co-Investigator at SJRCH.

Congratulations, Dr. Caudle!