Management of Patients With a Genetic Variant of Unknown Significance

Abstract

Accurate risk assessment of developing cancer often includes genetic testing for germline mutations, which has clinical and treatment implications for the patient and his or her family members. When a mutation is detected, aggressive measures for cancer prevention and detection are often implemented. Depending on the gene or genes tested, a variable percentage of patients will receive a test report stating that a variant of unknown significance (VUS) has been detected. This means that a change in the genetic sequence has occurred, but whether the change is associated with an increased risk of cancer or another disease is unclear or unknown. The results are confusing and noninformative. Oncology nurses will undoubtedly encounter patients with a VUS; consequently, they need to understand the controversies and ambiguities that surround these test results. Resources that may be offered by healthcare providers and aid in patient understanding of VUS results are available (see Figure 1).

Attitudes to and experiences of genetic information and testing among professionals working in the context of adoption

“…Social workers expressed concern that misunderstanding of genetic information may result in their misrepresenting information about the child when communicating with prospective parents. This supports current narratives regarding the importance of educating other professionals who are now using genetic information in mainstream medical care and encouraging links between the departments to improve clinical care (Mahon, 2015). Paediatricians, who often have clinical experience of genetic disorders, discussed the value of close communication with their local clinical genetics department.…”

Analysis of state laws on informed consent for clinical genetic testing in the era of genomic sequencing

“…A second related issue is that even variants that are not medically accepted as being associated with a disorder may be strongly suspected of being pathogenic or may be associated with conditions or behaviors that—while not constituting illnesses—are nevertheless stigmatizing (e.g., the association of the MAOA-L variant with impulsive and antisocial behavior (Fergusson, Boden, Horwood, Miller, & Kennedy, 2011)). Also, evolving scientific knowledge creates the possibility that the legal status of certain test results might be reclassified in the future (Mahon, 2015). This is problematic when genetic counselors need to know prospectively which tests are covered by genetic-specific informed consent statutes.…”

Understanding and interpretation of a variant of uncertain significance (VUS) genetic test result by pediatric providers who do not specialize in genetics

“…However, sequencing of multiple genes invariably results in more variants which cannot always be classified as pathogenic or benign. Depending on the genetic test, the laboratory performing the test, and the demographics of the patient, up to 20% of test reports contain a variant of uncertain significance (VUS), indicating there is a genetic sequence change but not enough evidence of whether the change is pathogenic or benign (Frank et al, 2002;Hall et al, 2009;Mahon, 2015). As genetic testing technologies expand to include untranslated and deeper intronic regions, laboratories may return more genetic test reports with VUS results (D. M. Eccles, Mitchell, et al, 2015;Lattimore et al, 2015).…”