Variant Interpretation in Current Pharmacogenetic Testing

Abstract

In the current marketplace, there are now more than a dozen commercial companies providing pharmacogenetic tests. Each company varies in the panel of genes they test and the variants they are able to screen for. The reports generated by these companies provide phenotypic interpretations of pharmacogenes and clinically actionable gene–drug interactions based on internally curated data and proprietary algorithms. The freedom to choose the types of evidence to include versus exclude in interpreting genomics has created reporting discrepancies in the industry. The case report presented here reveals the discordant phenotype analysis provided by two pharmacogenetic testing companies. The uncertainty and unnecessary distress experienced by the patient highlights the need for consensus in phenotype reporting within the industry.

Computational Tools to Assess the Functional Consequences of Rare and Noncoding Pharmacogenetic Variability

“…Furthermore, such providers take care of data security and privacy. Notably however, the processes underlying the generation of the result report are nontransparent, reporting and testing standards are heterogeneous, and interpretations can at times be discrepant between providers 12,13 …”

“…Notably however, the processes underlying the generation of the result report are nontransparent, reporting and testing standards are heterogeneous, and interpretations can at times be discrepant between providers. 12,13 The prevalence of rare pharmacogenetic variants has by now been well established; however, their functional interpretation remains challenging. While common candidate variants can be interrogated experimentally, mostly using heterologous expression systems, these methods are not sufficiently scalable for the analysis of tens of thousands of variants.…”

The pharmacogenetics of the new-generation antipsychotics – A scoping review focused on patients with severe psychiatric disorders

“…factors. Although the number of commercial companies worldwide producing pharmacogenomic test kits is increasing, each kit is different in the number and variety of the genes tested and the variants they are intended to screen for ( 25 ). Therefore, the reports resulting from the administration of such pharmacogenetic tests may be quite heterogenous, based on the evidence included or excluded by the manufacturers, leading to discordant phenotype analysis when tests originated in distinct companies are comparatively analyzed ( 25 ).…”

“…Although the number of commercial companies worldwide producing pharmacogenomic test kits is increasing, each kit is different in the number and variety of the genes tested and the variants they are intended to screen for ( 25 ). Therefore, the reports resulting from the administration of such pharmacogenetic tests may be quite heterogenous, based on the evidence included or excluded by the manufacturers, leading to discordant phenotype analysis when tests originated in distinct companies are comparatively analyzed ( 25 ). This indicates the need for continuous research dedicated to the validation of different gene-drug interactions and to the creation of consensus-based pharmacogenetic/pharmacogenomic evaluation strategies, in order to increase the homogeneity of the results and the possibility of finding the most appropriate monitoring tools for patients with SPD.…”

“…Although mental health specialists may be aware of pharmacogenomic testing, they may not be informed about all the advantages and limitations of this method. Therefore, increasing their awareness about pharmacogenomic testing can be very useful for patients with SPD, because, as stated above ( 25 ), implementing this type of testing can improve the quality of life, responsivity rate, and tolerability of psychiatric treatment.…”