Introducing a new publication from the Reactome team in the Database (Oxford) journal by Orlic-Milacic et al, titled "Pathway-based, reaction-specific annotation of disease variants for elucidation of molecular phenotypes"! 

The study outlines Reactome's expansion to encompass annotations for disease variants, providing insights into aberrant reactions and pathways caused by germline and somatic mutations. Aligning with the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) standards, Reactome classifies variants as benign or pathogenic, facilitating integration with other variant databases like ClinGen and ClinVar. Rather than exhaustively cataloging variants, Reactome focuses on characterizing the impact of representative variants on pathway activity, with annotations cross-referencing external resources such as OMIM and COSMIC. Despite the availability of computational tools, manual curation remains essential due to limitations in predicting functional impact and the narrow focus on missense variants.

The paper also introduces a protocol developed by the Reactome team for annotating variants in pathways, alongside an expanded dataset covering diverse classes of protein variants, including fusion proteins. These pathway-based annotations not only aid in identifying gaps in computational predictions but also enhance the interpretation and modeling of clinically relevant variants.

For other publications by the Reactome Team, visit our publications page.

Shown here is Figure 7: High-level graphical summary of Reactome’s ERBB2 cancer variants content. (A) Heatmap representation of Reactome electronic textbook knowledge on the sensitivity of different ERBB2 cancer variants to ERBB2-targeted anti-cancer therapeutics. The heatmap was generated using the R package pheatmap with default settings. (B) Interactive textbook style diagram for ‘Signaling by ERBB2 in Cancer’ pathway.