Receiving a genetic test result with a phrase like “heterozygous pathogenic variant” can be confusing. Understanding this result requires breaking down each component of the phrase. This guide will clarify the terminology, its relation to inheritance, and potential health implications to help you contextualize your genetic test results.
Decoding the Terminology
A gene is a set of instructions, much like a recipe in a cookbook, that tells the body how to function. A “variant” is a change in those instructions. While most variants are harmless or cause normal differences like eye color, some can affect how the instruction is read, similar to a typo that alters the final dish.
The term “pathogenic” is used to classify a variant as disease-causing. Geneticists classify a variant as pathogenic when there is strong evidence that it disrupts a gene’s function and leads to a health condition. This is different from a “benign” variant, which is harmless, or a “variant of uncertain significance” (VUS), which lacks enough evidence for classification.
“Heterozygous” means you have two different versions of a particular gene, having inherited one copy from each biological parent. A heterozygous result indicates that one copy of the gene has the pathogenic variant while the other copy is normal. This contrasts with being “homozygous,” which means you inherited the same variant from both parents, resulting in two altered copies.
Inheritance and Risk to Offspring
A heterozygous pathogenic variant often points to an autosomal dominant inheritance pattern. In this pattern, only one copy of the altered gene is needed to potentially cause a health condition. Because the gene is on a non-sex chromosome (autosome), it affects males and females equally.
An individual with this type of variant has a 50% chance of passing it on to each child, and this probability is independent for each pregnancy. It can be visualized like flipping a coin. Whether a child who inherits the variant develops the condition is a separate consideration related to penetrance and expressivity.
A pathogenic variant is not always inherited. A de novo variant is a spontaneous alteration that appears for the first time in an individual, occurring in the parent’s reproductive cells or during early development. Once an individual has a de novo variant, they can pass it to their children with the same 50% probability.
Health Implications and Disease Expression
Having a heterozygous pathogenic variant does not guarantee a person will develop the associated health condition. This is explained by “penetrance,” which is the statistical likelihood that someone with a pathogenic variant will show signs of the disease. Some variants have complete penetrance, meaning nearly everyone with the variant will develop the condition.
Other variants have reduced or incomplete penetrance, where only a certain percentage of people with the variant will get sick. For example, a variant with 80% penetrance means that eight out of ten people who have it will develop the associated health issues. Two people will not, despite carrying the same variant.
Another concept is “variable expressivity,” which describes the range of symptoms among people with the same pathogenic variant. Even within a family, individuals with the same variant can be affected differently, with some having mild symptoms and others having severe ones. This variability, along with penetrance, can be influenced by other genetic factors, environmental influences, and lifestyle choices.
Genetic Testing and Family Planning
After receiving a result with a heterozygous pathogenic variant, it is recommended to discuss the findings with a genetic counselor. These professionals are trained to explain the specifics of your result, what it means for your health, and the implications for relatives. They translate technical information into personalized guidance.
This knowledge can lead to cascade screening, which involves offering genetic testing to at-risk biological relatives. Identifying family members who carry the same pathogenic variant allows them to make informed decisions about their health. This may include pursuing preventive measures or increased surveillance.
For those who know they carry a pathogenic variant, this information can inform family planning. Options like preimplantation genetic testing (PGT) are available with in-vitro fertilization (IVF). PGT involves testing embryos for a specific genetic condition before uterine transfer, allowing parents to reduce the chance of passing the variant to their children.