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Chromosome spread

Variant of Uncertain Significance (VUS)

updated: July 1, 2022

Definition

When analysis of a patient’s genome identifies a variant, but it is unclear whether that variant is actually connected to a health condition, the finding is called a variant of uncertain significance (abbreviated VUS). In many cases, these variants are so rare in the population that little information is available about them. Typically, more information is required to determine if the variant is disease related. Such information may include more extensive population data, functional studies, and tracing the variant in other family members who have or do not have the same health condition.



Narration

Variant of uncertain significance or VUS. There is so much about the genome we don't know. Sometimes it seems we're just scratching the surface. In fact, the great majority of new variants that pop up in examining an individual person's genome can't definitely be classified as disease-causing or not and are called variants of unknown or uncertain significance. The more information scientists have about the variants seen in a specific family or group or population, the better they are at classifying them. And the number of VUS's in that population is lower than in others. At present, there is much more extensive genomic information about people of European ancestry than any other group leading to many more VUS's in those other groups that make it more difficult to identify disease causing variants. That's why it's critical for research studies to include more people of non-European ancestry so that people everywhere can benefit equally from genomic information.

Teri Manolio
Teri Manolio, M.D., Ph.D.

Director

Division of Genomic Medicine