Parental co-segregation analysis significantly reduces but does not eliminate VUS rate in multi-gene panel testing
Parental co-segregation analysis was informative in nearly 40% of cases, including 4/6 variants upgraded from variant of unknown significance (VUS) to likely pathogenic variant (VLP)
Gene-specific characteristics, such as reduced penetrance, variable expressivity, and multiple inheritance patterns, were the most frequent barrier to reclassification, accounting for 43% of variants that remained VUS
Authors: Elaine C. Weltmer; Tiffiney Carter; Jade Tinker; Amanda Bergner; Zöe Powis; Jing Wang