The Role of Variants of Unknown Significance in Diagnostic Yields

About 25% of our diagnoses were actually included in variants of unknown significance. The reason we did that was it was felt by both laboratories that these were variants within genes that were highly likely to be causing the phenotype. And so, I think rightfully we are all cautious about variants of known significance particularly if they've never been seen before. But when there is strong evidence, molecularly that these variants are disrupting protein function, or enaging that clearly could be causative for what we're seeing. So, that is not a real medicine that we really should be reporting them in our diagnostic yields. Most papers in the field do not do this and we recognize that could be a limitation moving forward.