Genetic Testing Results: Variant of Uncertain Significance (VUS) & De Novo
What's UP Doc? Is a regular column where we feature a patient question along with a response from a member of the UPA Scientific Advisory Board.
I was diagnosed with AIP based on my lab results, but my genetic test shows a VUS and I was told the variant is de novo. Can you explain what a VUS means in my case, what ‘de novo’ means, and whether this variant could also be found in people outside my family?
Today’s answer comes from Dr. Hetanshi Naik of the Stanford University School of Medicine, CA.
VUS stands for variant of uncertain significance. In your case, it means that the genetic test found a change (variant) in the gene that is known to cause AIP, however the lab does not have enough information to confidently say whether the variant found causes AIP or is a benign change.
On its own, the result of VUS on a genetic test for AIP is inconclusive. Results from biochemical testing- specifically substantially increased urine PBG- is needed to confirm a diagnosis.
Learn more about VUS
Learn more about porphyria testing
De novo means the genetic change (variant) found in you was not inherited from one of your parents, which is what usually happens with AIP. The change is “new” and happened for the first time in you. The variant found could be found in people outside your family, the same change that happened to your gene could happen independently to other people who are unrelated to you.
Learn more about de novo variants
Disclaimer
What’s UP Doc? is not intended as medical guidance for individual patients. Any individual care decisions should be made in consultation with your healthcare team. Please contact United Porphyrias to locate a physician in your area, to provide information about porphyria to a current physician, to advise about referral to a specialized porphyria center, or to arrange a peer-to-peer consult between your physician and a porphyria specialist, contact UPA at 800-868-1292 or info@porphyria.org.
Thank you to Dr. Naik for this What's UP Doc? answer! Do you have a question for a porphyria expert? Send it to info@porphyria.org.
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