Penetrance

There are very few genotypes (having a particular genetic variant) that always result in the associated phenotype (in healthcare, the signs and symptoms of a condition). This can make determining inheritance patterns more difficult: family members may have the genotype but no signs or symptoms of the condition under investigation.

When a genotype always leads to a particular phenotype, it is known as complete penetrance. An example is Huntington’s disease, in which the disease-causing variant is 100% penetrant. This is unusual, however: most disease-causing variants are not completely penetrant.

There are many disease-causing variants that have high but not complete penetrance. For example, some familial hypercholesterolaemia variants have penetrance of more than 90% – meaning that 9 in 10 people with those variants will develop familial hypercholesterolaemia.

Other variants are important causes of disease but have lower penetrance. For example, BRCA2 gene variant penetrance can be as low as 47% depending on the population.

With genotypes that are not 100% penetrant, it is not possible to predict who will develop the condition and who will not.

Penetrance can only be determined by large population studies. The more people with a variant who can be assessed for presence or absence of the associated phenotype, the more accurate the penetrance estimate will be.

• There are very few genotypes that are completely penetrant.
• Incomplete penetrance occurs when not all individuals with a genotype have the associated phenotype.
• Penetrance can only be determined by large population studies.

• Henderson R, O’Kane M, McGilligan V and others. ‘The genetics and screening of familial hypercholesterolaemia‘. Journal of Biomedical Science 2016: volume 23, issue 39. DOI: 10.1186/s12929-016-0256-1
• Zhang LJ, Shin VY, Chai X and others. ‘Breast and ovarian cancer penetrance of BRCA1/2 mutations among Hong Kong women‘. Oncotarget 2018: volume 9, issue 38, pages 25,025–25,033. DOI: 10.18632/oncotarget.24382