* PGx alleles on Excel-style formats , also accessible through the PharmGKB API (seems to be hidden from the PGRN Translational Pharmacogenetics Project (TPP)Swagger documentation, published through but direct links when searching for haplotype definitions at the pharmgkb.org website)* [https://apigithub.com/PharmGKB/PharmCAT/tree/master/src/main/resources/org/pharmgkb/pharmcat/definition/alleles PGx alleles for use in PharmCAT] are included in their source code.org PharmGKB APIIt is reasonable to suspect that these files are parsed from the Excel files.* [https://github.com/inumanag/aldy/tree/master/aldy/resources/genes PGx alles for use in Aldy]are included in their source code. Due to the lack of GRCh37 variant definitions for CYP2D6, Aldy has likely lifted over GRCh38 variants to GRCh37. The Aldy developers have also added new star alleles with (non functional) variants that are often observed together with the main star allele.

 ==How to chose the correct PGx allele definitions=====Chosing an appropriate genomic reference build===PGx allele definitions are given in either GRCh37 or GRCh38 reference coordinates. * PharmCAT, CPIC and PharmGKB as a rule use build GRCh38. * Aldy uses GRCh37. * The process of changing from PharmGKB API as a rule is using GRCh37 alleles, but not for all variants. Moreover, the build is given as "hg38", even when the actual coordinates are mostly GRCh37 (hg19). In the PharmGKB and CPIC Excel sheets, however, the move to GRCh38 for is completed.  As is evident from liftOver, hg19 is not equal to GRCHh37, nor hg38 to GRCHh38. This could also be a source of error. ===Chosing the correct variants to include in the PGx alleles===The allele definitions from PharmGKB and PharmVar are not always one-to-one, and some background knowledge about why this is only partially completed, is required.  Additional prefiltering of PharmGKB or PharmVar allele definitions by domain experts may be needed. * Prefiltering was performed by the [[PGx in Estonia|PGx pipeline of the University of Tartu]], and a list of the resulting variants were published in the supplementary material to [https://www.biorxiv.org/content/early/2018/07/04/356204 ''Reisberg et al.'']. The variants per star allele are, however, not written out explicitly.* Prefiltering was performed on allele definitions in Aldy and the [https://github.com/inumanag/aldy/tree/master/aldy/resources/genes result published in their code].We suspect An example that there illustrates many definition problems is CYP2C19*19: {| class="wikitable"|-! CYP2C19*19 !! PharmGKB !! PharmVar !! PharmCAT !! Comment|-| NC_000010.10(GRCh37) || Source API: g.96522561T(rs17885098), g.96602623G(rs3758581), g.96522613A>G, g.96609568T>C(rs4917623)|| Source VCF: g.96521422A>G(rs7902257), g.96522613A>G || Source GitHub: g.96522613A>G(by liftOver) || Disagree on rs4917623(intron), rs7902257(2kb upstream variant). rs17885098 and rs3758581 are serious discrepancies included here because PharmGKB assume different reference bases for these positions (seems like a problem caused by change of Major allele between PharmVar reference builds GRCh37/GRCh38. Note that refSeq also agrees with GRCh38 and not GRCh37)|-| NC_000010.11(GRCh38) || Source Pharmgkb.org: g.94762856A>G || Source VCF: g.94762804C>T(rs17885098), g.94762856A>G, g.94842866A>G(rs3758581) || Source GitHub: g.94762856A>G || PharmGKB sources does not agree with itself when reporting GRCh38 variants on the homepage and GRCh37 variants in the API. The differences probably caused by non-standard use of Major/Minor Allele (rs17885098, rs3758581) with respect to dbSNP, and removing intron variants (rs4917623) may be sensible from an exon/protein-coding view.|} The main problem with the changes in definitions is that the same patient may be given different PGx-advice depending on the build version of the pipeline (which unless of course that the haplotype is strange as PharmGKB gets data form PharmVaralways conserved) Comparisons between PGx genotyping tools can give some insight into the accuracy of allele definitions. In Aldy they have [https://github.com/inumanag/aldy-paper-resources compared their method to targeted sequencing] with good results.

As we saw in the previous section, PGx alleles are defined as collections of one or more SNPs, INDELs or structural variants. When a patient is sequenced by next generation sequencing ([[NGS]]) technology we may typically observe more variants than those which are included in any individual PGx allele definitions.