Why a variant of uncertain significance isn’t a diagnosis

Variants & interpretation · 2 min read · Updated 30 July 2026
In brief

Uncertain means the evidence is incomplete. Guidelines say not to act on a VUS, and most are eventually reclassified as benign.

A variant of uncertain significance is a change we can see clearly but cannot interpret confidently. The evidence is genuinely split or thin - that is the whole meaning of the term.

Clinical guidelines are explicit that a VUS should not be used to make medical decisions or to change screening. Most VUS findings are eventually reclassified as benign.

A VUS is worth discussing with a clinician who knows your family history, because family history changes what the same variant implies.

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