Tiers

Variants of potential relevance to the patient’s clinical presentation will be automatically categorised into one of three tiers:

Tier 1

Includes, high impact variants (e.g., likely loss-of function), de novo moderate impact variants (e.g., missense) and variants with known pathogenic/likely pathogenic disease associations within the curated list of Green genes in the panels applied for analysis (available through PanelApp).

Tier 2

Includes moderate impact variants (e.g., missense) within the curated list of Green genes in the panels applied for analysis (available through PanelApp).

Tier 3

Plausible candidate variants identified with high or moderate impact or with known pathogenic/likely pathogenic disease associations in genes OUTSIDE those included in the analysis panel(s). Caution should be used during clinical assessment and interpretation. Although most tier 3 variants will NOT be pathogenic, sometimes the causal variant will lie within tier 3. This could occur because there is insufficient evidence to support the inclusion of the gene within the relevant panel(s) at the time of analysis, or because the relevant panel was not applied.

Note

Occasionally a diagnostic variant may not be tiered, for example if the segregation pattern (disease status) provided in the test order tool for sequenced family members is inconsistent with the segregation pattern of variant(s).