OA: Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer - The Journal of Molecular Diagnostics

The Journal of Molecular Diagnostics

 Article Outline

1. Databases
   1. Genomic Databases
   2. Reference Sequence Databases
   3. Population Databases
   4. Cancer-Specific Databases
   5. Constitutional Variant Databases
   6. Internal (Laboratory-Generated) Databases
2. In Silico (Computational) Prediction Algorithms
3. Variant Identification and Annotation
4. Proposed Guideline for Evidence-Based Categorization of Somatic Variants
   1. Tier I Variants: Variants with Strong Clinical Significance (Level A and B Evidence)
      1. Variants with Level A Therapeutic Significance
      2. Variants with Level A Diagnostic/Prognostic Significance
      3. Variants with Level B Therapeutic Significance
      4. Variants with Level B Diagnostic/Prognostic Significance
      5. Germline Pathogenic Variants Associated with Cancer Predisposition
   2. Tier II Variants: Variants with Potential Clinical Significance (Level C and D Evidence)
      1. Variants with Level C Therapeutic Significance
      2. Variants with Level C Diagnostic/Prognostic Significance
      3. Variants with Level D Therapeutic Significance
   3. Tier III Variants: Variants of Unknown Significance
   4. Tier IV Variants: Benign or Likely Benign
   5. Germline Variants Identified during Cancer Testing
5. Interpretation and Reporting
   1. Tier-Based Reporting
   2. Nomenclature
   3. Other Reporting Elements
   4. Reporting of Germline Variants
   5. Reporting the Clinical Significance of Detected Variants
   6. Updating Knowledge
   7. Reporting Method
   8. Integration with Electronic Health Records
6. Conclusion
7. Disclaimer
8. Supplemental Data
9. References

 It is our hope that the guidelines presented herein will achieve widespread use in the cancer genomics community and engender significant improvements in the practice of genomic testing and precision care for cancer patients.