In the case of CF, examined in this work, the limitations observed in the LQTS and ARVC examples are largely overcome through the use of: expert consensus on pathogenic CFTR variant calls, a clinical data source (i.e. Geisinger’s EHR) where comprehensive diagnostic phenotyping and clinical genetic testing of suspected cases is common, and a gene-disease example with clearly established diagnostic criteria that are routinely interrogated by expert clinicians in suspected cases. Here, CFTR is linked to cystic fibrosis.