Tiers¶
Variants of potential relevance to the patient’s clinical presentation will be automatically categorised into one of three tiers:
Tier 1¶
Rare variants that impact 'Green' genes (see PanelApp) in the applied gene panel, that are:
- high impact variants (e.g., likely loss-of function) that impact 'Green' genes in the applied gene panel;
- de novo moderate impact variants (e.g., missense);
- de novo variants in non-coding genes; or
- variants with known pathogenic or likely pathogenic disease associations
Tier 2¶
Rare variants that impact 'Green' genes (see PanelApp) in the applied gene panel, that are:
- moderate impact variants (e.g., missense) in a gene biotype considered for tiering; or
- a non coding exon transcript variant in a non-coding gene
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).
Note
Variants in non-coding genes outside of the applied gene panel are not included in Tier 3 variants.