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Variant of Uncertain Significance (VUS) - National Human Genome . . . 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)
I have a VUS (Variant of Uncertain Significance) Now what? - Mayo Important advice on your VUS: • Do not assume the worst • Having a VUS and a medical diagnosis does NOT mean they go together • Remember, we all have thousands of DNA variants and most are entirely unrelated to our health situations • There may be more harm done in wrongly assuming a VUS is harmless or harmful
What’s a “Variant of Uncertain Significance?” A VUS? It’s in a “breast cancer cluster region” of DNA bases 179 through 505, but lies outside the hotspot of bases 72-192 The VUS designation means that hardly any variants have turned up that match the one in Annie’s daughter, so it can’t definitively be called benign or likely benign
Uncertain significance in somatic cancer panel testing Somatic cancer panel testing often identifies variants of uncertain significance (VUS), whose effects on cancer cells are unclear The clinical significance of a VUS may be uncertain due to limited data, conflicting evidence, or its varying role across different cancer types
Assessing a Variant of Uncertain Significance (VUS) Figuring out if a VUS falls more on the benign or pathogenic side is the first step in determining how to discuss it with a patient and whether to pursue further investigation VUS
Understanding genetic variants of uncertain significance Variants with insufficient or conflicting evidence supporting disease association, such that they cannot be classified as ‘pathogenic likely pathogenic’, nor as ‘benign likely benign’, are VUSs The presence of a VUS, even in a relevant gene or chromosome, does not confirm a genetic diagnosis
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