This tier model attempts to adopt concensus recommendations by ACMG, as outlined in Li et al., 2017:
- Tier 1: Variants of strong clinical significance - constitutes
variants linked to predictive, prognostic, or diagnostic biomarkers
in the CIViC database and the
Cancer Biomarkers
Database that
are
- A: found within the same tumor type/class as specified by the user, AND
- B: of strong clinical evidence (i.e. part of guidelines, validated or discovered in late clinical trials)
- Tier 2: Variants of potential clinical significance - constitutes
other variants linked to predictive, prognostic, or diagnostic
biomarkers in the CIViC database
and the Cancer Biomarkers
Database that
are either
- A: of strong clinical evidence in other tumor types/classes than the one specified by the user, OR
- B: of weak clinical evidence (early trials, case reports etc.) in the same tumor type/class as specified by the user
- Tier 3: Variants of uncertain clinical significance - includes other coding variants found in oncogenes or tumor suppressor genes
- Tier 4 - includes other coding variants
For copy number aberrations, aberrations linked to Tier 1 & 2 are displayed, within following sections in the HTML report:
- Copy number aberrations as biomarkers: Aberrations of strong clinical significance (Tier 1)
- Copy number aberrations as biomarkers: Aberrations of potential clinical significance (Tier 2)