Assessing management practices for variants of uncertain significance among genetic counselors in pediatrics

Abstract

AbstractIncreased utilization of genomic sequencing in pediatric medicine has increased the detection of variants of uncertain significance (VUS). Periodic VUS reinterpretation can clarify clinical significance and increase diagnostic yield, highlighting the importance of systematic VUS tracking and reinterpretation. There are currently no standardized guidelines or established best practices for VUS management, and our understanding of how genetic counselors (GCs) track and manage VUS results for pediatric patients is limited. In this exploratory study, GCs in pediatric clinics in North America were surveyed about their VUS management practices. A total of 124 responses were included in the analysis. The majority (n = 115, 92.7%) of GCs reported that VUS management workflows were at the discretion of each individual provider in their workplace. Approximately half (n = 65, 52%) kept track of patient VUS results over time, and GCs with lower patient volumes were more likely to do so (p = 0.04). While 95% (n = 114) of GCs had requested VUS reinterpretation at least once, only 5% (n = 6) requested it routinely. Most (n = 80, 86%) GCs notified patients when a VUS was reclassified, although methods of recontact differed when the reclassification was an upgrade versus a downgrade. GCs who asked patients to stay in touch through periodic recontact or follow‐up appointments were more likely to request VUS reinterpretation (p = 0.01). The most frequently reported barriers to requesting reinterpretation regularly were patients being lost to follow‐up (n = 39, 33.1%), insufficient bandwidth (n = 27, 22.9%), and lack of standardized guidelines (n = 25, 21.2%). GCs had consistent overall practices around VUS management around investigation, disclosure, reinterpretation, and recontact, but specific methods used differed and were at the discretion of each provider. These results showcase the current landscape of VUS management workflows in pediatrics and the challenges associated with adopting more uniform practices. The study findings can help inform future strategies to develop standardized guidelines surrounding VUS management.