How many genetic variants do we have?
VUS: Variant of Uncertain Significance. What is that?
Why do we care about VUS?
How do we finally determine the real significance of a VUS?
VUS and preconception screenings
A common misconception regards the imaginative power of high-throughput sequencing (i.e. whole exome sequencing and whole genome sequencing) in preconception screenings. Some believe that doing whole exome or whole genome sequencing before having a baby will protect them from having a genetic disease at birth. This is absolutely not true and the reason is right the presence of VUS.
We're all healthy carrier of several genetic disorders, which can be transmitted in an autosomal recessive or X-linked recessive manner (i.e. disorders that can be transmitted to the progeny by two parents which are unaffected healthy carrier or by a mother who is unaffected healthy carrier and may conceive affected males). Because several pathogenic mutations for rare disorders have been deposited in the literature, we can isolate them in preconception screenings and consequently calculate the reproductive risk for those specific mutations. However, we'll always be carriers of additional pathogenic mutations which can't be defined pathogenic a priori, because they are VUS.