Assessment of a Highly Curated Somatic Oncology Database to Aid in the Interpretation of Clinically Important Variants in Next-Generation Sequencing Results

J Mol Diagn. 2020 Nov;22(11):1356-1366. doi: 10.1016/j.jmoldx.2020.08.004. Epub 2020 Sep 19.


This study evaluated the accuracy of NAVIFY Mutation Profiler, a cloud-based CE-IVD software that aids in interpreting clinically relevant variants detected in somatic oncology next-generation sequencing tests. This tool reports tiered classifications based on different levels of clinical evidence from a highly curated, regularly updated database derived from medical guidelines, drug approvals, and peer-reviewed literature. A retrospective analysis was performed on next-generation sequencing results from 37 lung cancer cases treated with chemotherapy (n = 10), EGFR tyrosine kinase inhibitor (TKI) (n = 5), or ALK TKI (n = 22). Several aspects were assessed, including accuracy of interpretation compared with manual curation, validity of curation content updates over time, and agreement with public databases. For chemotherapy cases with no targetable biomarkers, NAVIFY Mutation Profiler did not identify any targeted therapies. In EGFR and ALK TKI cases, the software associated appropriate targeted therapies and accurately interpreted variant combinations containing drug-resistance variants. Of the nine unique ALK mutations conferring resistance to crizotinib, NAVIFY Mutation Profiler provided correct annotation for all mutations, whereas OncoKB and Catalogue of Somatic Mutations in Cancer indicated crizotinib resistance for eight of nine mutations. For 145 variants analyzed, NAVIFY Mutation Profiler and OncoKB showed substantial agreement (Cohen κ = 0.62) for classifying actionable mutations. Furthermore, NAVIFY Mutation Profiler presented accurate targeted therapies across different regions and remained up-to-date with evolving regional approvals and medical guidelines.

MeSH terms

  • Adenocarcinoma of Lung / blood
  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / genetics*
  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase / genetics
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Circulating Tumor DNA / blood
  • Circulating Tumor DNA / genetics
  • Crizotinib / therapeutic use
  • Databases, Genetic*
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Mutation
  • Polymorphism, Single Nucleotide
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies
  • Software*
  • Treatment Outcome


  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • Protein Kinase Inhibitors
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors