While genomic medicine is becoming an important part of patient care with an ever-increasing diagnostic yield, recontacting patients after reclassification of variants of uncertain clinical significance (VUSs) remains a major challenge. Although periodical reinterpretation of VUSs is highly desired, recontacting former patients with new classifications is commonly not fulfilled in practice. We draw on semi-structured interviews with 20 Israeli healthcare professionals and stakeholders involved in communicating the results of genome-wide sequencing to patients. Findings show agreement that an individual health care professional cannot address the task of recontacting patients after re-classification, and that responsibility should be shared among the medical specialties, laboratory scientists, as well as patients. In the absence of established guidelines, many respondents suggested that the patient should be informed about reclassification during a follow-up contact but they disagreed who should be responsible for informing the patient. HCPs agreed that the solution to this challenge involves a centralized automated database that is accessible, continuously updated, and facilitates retrospective as well as prospective flagging of reclassification for patients who can benefit from this information. National and international policies providing concrete guidelines on the optimal way to recontact patients with new valuable genomic information are needed.
New technologies of DNA sequencing produce increasingly more high-resolution genetic data. Next-generation sequencing technologies provide in a single test more data on more genes or regions in the genome than the earlier sequencing technologies. Consequently, variants of uncertain significance are found more often, leading to a continuous process of re-interpreting and reclassifying genetic variants as either benign or pathogenic. Recent research suggests that about 8% of the variants initially classified as variants of uncertain clinical significance (VUSs) were later reclassified: either downgraded to less severe classification (about 91% of variants) or upgraded to more severe classifications (about 9% of variants, see Mersch et al., 2018). Reclassification is based on new information regarding variants' pathogenicity, such as population frequency, functional data, segregation analysis, and phenotype analysis. Periodical reinterpretation of VUSs is therefore inevitable yet involves collaboration among multiple stakeholders: public and private genetics laboratories, clinicians, genetic health professionals, and medical geneticists (Carrieri et al., 2017). It is challenging for healthcare professionals (HCPs) to remain abreast of VUS reclassification.Communicating and interpreting VUSs is trying for both pa-
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