Questions remain regarding the strength and amount of evidence needed to sway a classification from a VUS to P/LP or B/LB. Since in clinical settings substantial evidence is needed to reach a P/LP classification, we have opted to use in silico algorithms exclusively to shift a VUS classification to LB.27 We require additional evidence (genotype, phenotype, family history, segregation, and functional studies) to upgrade a VUS to a P or LP variant.