Variant of Uncertain Significance (VUS)

Genetic tests are a way to look for specific differences (variants) in a person’s genetic information. Genetic information tells a person’s body how to grow and function. “Genes,” “DNA,” and “chromosomes” are all genetic information. All people have genetic variants, which makes them unique individuals. Some variants can have more of an impact on health and development.

There are 2 kinds of genetic tests:

• Chromosome tests look at your chromosomes to see if there are any extra or missing pieces or copies. Chromosomes are packages of genes in our cells. If there is anything extra or missing, it is a chromosome disorder.
• Gene tests, also called molecular tests, look at individual or groups of genes for mutations or “spelling errors” that could lead to a specific genetic disorder.

• Normal/Negative: This result means that the test did not find any variants in the chromosomes or genes that were tested. This could mean that your child is not affected by a particular disorder, does not have an increased risk of developing a certain disorder, or is not a carrier of a specific genetic variant. However, one kind of test cannot look for every possible genetic change, so it is possible that your child may need more testing to look at other genes.
• Abnormal/Positive: This result means that a change was found in your child’s genes. This usually will diagnose a genetic disorder, confirm that your child is a carrier, or identify an increased risk of developing a health condition.
• Variant of uncertain significance (VUS): A variant of uncertain significance (VUS) means that a variant was found, but there is not enough information to know if it causes symptoms or is benign. If a child’s genetic parents (or other closely related genetic relatives) are also tested, the chance for a VUS result is decreased. It is more common to find this test result when testing multiple genes at once.

Not necessarily. Many variants do not negatively impact a person’s health (benign). Humans have more than 50 million variants, some are responsible for normal variants, like our eye or hair color.

Some variants are associated with a genetic disorder (pathogenic). A VUS can be frustrating, because it is unclear how that genetic change affects your child. Even though a VUS may not provide a clear answer, there are still steps that you can take with your child’s medical providers.

Because it is not clear how a VUS affects your child, treatment should be based on their personal and family history. Scientists are doing research on genetic changes in other people to help understand how they are associated with genetic disorders.

Your child’s healthcare provider is the best way to learn if more information is found about your child’s genetic change, so we encourage you to stay in touch over the years by calling or scheduling an appointment.

Sometimes we recommend testing for genetic parents. In some cases, including other closely related genetic relatives (like siblings or grandparents) is helpful. Samples from genetic parents can help medical providers understand your child’s test results, showing us if the variant is passed down (inherited) or new in the child.

• If a genetic parent has the same VUS, but does not have the same symptoms or disorder, the variant is less likely to be the cause of a disorder (benign). However, sometimes a parent shows fewer signs of a condition than a child.
• If a genetic parent has the same VUS, and has the same symptoms or disorder, it is likely that the variant is the cause of a disorder (pathogenic).
• If neither genetic parent has the same VUS, and it is a new change in your child (de novo), it is likely that the variant is the cause of the disorder (pathogenic).

The medical provider or genetic counselor can talk with you about who should be included on follow up genetic testing for a VUS.

Genetic tests are often expensive and might not be covered by insurance. Without pre-authorization, you may have to pay for the test yourself. To learn more, read our handout “Insurance coverage for Genetic Testing” seattlechildrens.org/pdf/PE2051.pdf

A genetic counselor is available to talk about this with you. Contact the Medical Genetics clinic to speak to a genetic counselor or schedule an appointment at 206-987-2056.