How to Read an Inherited-Cancer Genetic Testing Report

What Was Tested

The report should list the genes analysed and the type of analysis: full sequencing, large-rearrangement (deletion and duplication) analysis, or targeted testing for specific known variants. A gene that was not on the panel was not assessed.

It should also state the sample type, usually blood or saliva, confirming that this is a germline (constitutional) test rather than a tumour test.

The Five-Tier Classification

Variants are classified as pathogenic, likely pathogenic, uncertain significance, likely benign or benign. Only pathogenic and likely pathogenic variants are considered clinically actionable.

A variant of uncertain significance means the evidence is currently insufficient. It is not a partial positive and should not by itself prompt changes in screening or surgery.

Positive, Negative and Uninformative

A positive result identifies a pathogenic or likely pathogenic variant. A true negative applies when a specific familial variant was tested for and not found; the person's risk then usually returns to population level.

An uninformative negative, where no variant is found but no familial variant was known, does not exclude hereditary risk, especially with a strong family history.

Gene-Specific Meaning

The implications of a pathogenic variant depend on the gene. High-risk genes such as BRCA1, BRCA2 and the mismatch-repair genes have established surveillance and risk-reduction pathways. Moderate-risk genes such as ATM and CHEK2 usually mean enhanced screening with family-history-adjusted risk.

The report's management recommendations are general; individual decisions are made with a clinical genetics or oncology team.

Interpretation Notes

Classifications can change over time. Laboratories may reclassify a variant as new evidence accumulates and reissue the report, so the report date matters.

Secondary or incidental findings in genes unrelated to the test indication are handled according to the laboratory's stated policy and consent.

Key Takeaways

• ·Check which genes and which analysis types were actually performed.
• ·Only pathogenic and likely pathogenic variants are actionable; a VUS is not.
• ·A true negative requires a known familial variant to test against.
• ·Management implications depend on the specific gene and are finalised with a specialist.