Table 2 Major policy issues

Duty to re-contact

To what extent healthcare providers have a duty to re-contact patients in the case of a reclassified VUS

• EHRs and integration of genomic data into EHRs

• Rely on patient to request new interpretation

• Patient access to databases

• Formulate standard practices for re-contact

• Integrate notification of users (health professionals, counselors or consumers) into databases, websites and interpretive software

Informed consent

Considerations and options within the informed consent process

• Broad consent

• Opt out option for some results

• Options for re-contact integrated into consent process

Patient understanding

How to reduce uncertainty introduced by VUS results that can lead to misunderstanding by patients and professionals

• Careful pretest counseling with qualified genetic counselors or other health professionals

• Education of clinicians, counselors and consumers

• Resources to assist consumers in interpreting test results

Data sharing

How to aggregate data on VUS from disparate clinical and research laboratories, particularly those performing gene panel or WES/WGS analyses

• Centralized open-access database

• Make deposition of data and methods sufficient to enable independent verification a condition of payment

• Accreditation of laboratories contingent on independent verification and data sharing

• Condition of certification for laboratory directors and/or genetics health professionals

Research to improve VUS interpretation

How to improve the evidence base for interpretation of genomic variants

• Public and private research programs

• Individual research projects

• Consortia and formal research networks

• Studies of ethical, legal and practical experience in using gene panels and WGS/WES analysis