Table 1. Differences between high-penetrance Mendelian gene mutations and SNPs analyzed by DTC genomic testing.

RR, relative risk (relative risk of developing a disease in a given population); CLIA, Clinical Laboratory Improvement Act; CAP, College of American Pathologists.

High-penetrance mutationsDTC trait-associated SNPs
Proportion of disease due to mutations or variantsHigh (typically >70%)Low (1 to 3%)
Attributable risksHigh (RR > 2, typically RR > 10)Low (RR, 1.01 to 1.3)
Analytic validityClose to 100% (for laboratories with CLIA certification and CAP accreditation)Variable
Clinical validityFound with high probability in individuals with disease; never or rarely found in normal individualsSame SNPs found in individuals with disease or trait and in controls (but in different proportions)
Clinical utilityUsed as molecular diagnostic and as predictive testTypically not clinically useful
ActionabilityOften changes or informs medical management, such as indicating organ-specific surveillanceNot actionable; attributable risks are too low