Change Log

Starting in March 2024, this page highlights the major content updates. For more detail, visit the PharmCAT GitHub Releases page.

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v2.11.0

F5

DPWG removed the recommendation for F5 and the hormonal contraceptives for systemic use. The guideline annotation was retired on PharmGKB, which removes F5 from PharmCAT.

v2.10.0

DPYD

DPYD HapB3 is defined by two variants, c.1129-5923C>G (an intronic variant) and c.1236G>A (an exonic variant). PharmVar and CPIC now include and list the variant c.1129-5923C>G separately as this is likely the causal variant leading to a decreased function. CPIC still retains the DPYD HapB3 haplotype definition for cases where only the exonic variant c.1236G>A is tested (e.g. whole-exome sequencing). For more information, see CPIC Guideline for fluoropyrimidines and DPYD.

This change prompted the following PharmCAT updates:

  • If c.1236G>A (the exonic defining variant of DPYD HapB3) is missing, PharmCAT will use the intronic variant c.1129-5923C>G.
  • If c.1129-5923C>G and c.1236G>A do not agree, PharmCAT will use c.1129-5923C>G and also report the presence of c.1236G>A in the input.
  • DPYD HapB3 will be reported if both of its defining variants c.1236G>A and c.1129-5923C>G are present and “in sync” with each other in the input VCF file.

RYR1

In December 2023, CPIC has added additional 291 variants that were included in the ClinGen variant curation expert panel (VCEP) recommendations for RYR1 pathogenicity. PharmCAT accommodates these changes by updating the Named Allele Matcher module. The Name Allele Matcher now will report all RYR1 variants found in an individual.

CPIC RYR1 phenotypes are determined based on the function combinations of two RYR1 variants. PharmCAT will prioritize the variants with Malignant Hyperthermia-associated function for individuals with more than two variants. If the input VCF file is not phased, PharmCAT assumes an individual to have two or more Malignant Hyperthermia-associated variants on different chromosomes. PharmCAT prioritizes variants with Malignant Hyperthermia-associated function when determining the RYR1 phenotype for an individual.

PharmCAT is managed at Stanford University & University of Pennsylvania (NHGRI U24HG013077).