Which repeat size category indicates a pathogenic variant in Huntington Disease?

In Huntington Disease, the number of CAG repeats in the HTT gene is critical for understanding disease risk and pathogenicity. A repeat size of 40 or more CAG repeats is unequivocally considered a pathogenic variant. This level of repeats is associated with the full penetrance of the condition, meaning individuals with 40 or more repeats will almost certainly develop symptoms of Huntington Disease if they live long enough.

The repeats in the 36-39 range can be considered inconclusive; individuals with this number of repeats may or may not develop the disease, thus this category is often referred to as the "grey zone." The 27-35 repeat range is viewed as intermediate and again does not guarantee disease manifestation. Lastly, the 10-26 CAG repeats are considered normal and not associated with the disease. Understanding these classifications helps clinicians evaluate patient risk and manage their care appropriately.