Table 3.

Key questions related to genome-scale test examples

Case 1: exome testing in work-up of a child with neurocognitive and/or developmental problems
Appropriate candidates for testing	What clinical or laboratory evaluation should be undertaken prior to testing? What is the optimal age for testing?
Trio evaluation	What clinical presentations are best evaluated with trio testing?
Secondary findings	What are the pros and cons of seeking specified secondary findings?
Variants of uncertain significance (VUS) and pathogenic or likely pathogenic findings unrelated to clinical presentation	What pretest counseling is recommended related to the possibility of VUS and findings unrelated to clinical presentation? What laboratory and clinical follow-up is recommended for each?
Case 2: patient with a strong family history of breast cancer
Scope of gene panel	What are the relative benefits and harms of more inclusive vs. less inclusive panels?
Implications of patient characteristics	Should panels differ for patients with cancer vs. those being tested for a positive family history? How should family history or other patient characteristics influence the scope of the panel?
Moderate risk variants	What are the pros and cons of including genes associated with moderate risk?
Variants of uncertain significance (VUS) and pathogenic or likely pathogenic findings unrelated to clinical presentation	What pretest counseling is recommended on the possibility of VUS and findings unrelated to clinical presentation? What laboratory and clinical follow-up is recommended on each?
Clinical follow-up	What interventions should be informed by test results?