Commonly performed genetic testing (explain results only) - reduced penetrance

Definition

Penetrance describes the proportion of individuals carrying a pathogenic variant who go on to express the associated phenotype - reduced (incomplete) penetrance means some carriers remain asymptomatic despite carrying a variant fully capable of causing disease
Common across many autosomal dominant conditions (e.g. BRCA1/2, hereditary cardiac conditions such as hypertrophic cardiomyopathy and long QT syndrome) - true 100% penetrance is relatively unusual for most dominant conditions

Penetrance is influenced by modifier genes, environmental factors, and (for some conditions) age ("age-related penetrance" - risk of expressing the phenotype rises with age, meaning an asymptomatic young carrier may still develop disease later) - it is rarely a fixed, binary property of the variant alone

Reduced penetrance complicates family counselling - an asymptomatic relative who tests positive for a familial pathogenic variant carries genetic risk even without current symptoms, and "unaffected" family members in a pedigree may still be carriers, which can obscure the inheritance pattern if penetrance is not considered

Genetic counselling for a reduced-penetrance condition must communicate risk, not certainty - a positive result means increased risk of developing the condition (and of passing the variant to offspring), not a guaranteed diagnosis
Surveillance/risk-reducing strategies are still generally offered to asymptomatic carriers of a variant in a reduced-penetrance condition, since risk remains elevated even without current symptoms

BRCA1/2 (breast/ovarian cancer risk), hypertrophic cardiomyopathy, long QT syndrome, hereditary cancer syndromes generally

Reduced penetrance is a key reason a "negative" family history does not exclude a hereditary condition - an unaffected parent can still have transmitted a pathogenic variant to their child without ever expressing the phenotype themselves

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