FIGURE 4.

Threshold model of disease. Some deleterious monogenic variants are sufficient to cause the disease alone and do not need any genetic modifiers to cause the disease phenotype. Other monogenic variants may be incompletely penetrant and only display a disease phenotype when accompanied by other genetic or non-genetic factors that raise them above the clinical threshold for disease presentation. In the latter scenario, individuals may have the same underlying causal variant but have very different phenotypic presentations depending upon their modifying factors.