Table 2.

Technical and practical challenges of genomic testing in the clinic

Technical

Accurate and efficient analytic assessment of genomic variants (increase its clinical validity and utility)

Better coverage of certain genomic regions (<50 %)

Need for result confirmation (i.e. by Sanger sequencing)

Handling of variants of uncertain significance (VUS) and novel variants (when reporting to clinicians and disclosing results to patients)

Need for expert knowledge on each gene and disease, improved information on rare gene variants freely available in public databases

Practical/operational

Disclosure of “incidental findings” and its familial implicationsa

Segregation studies in families to investigate the pathogenicity of novel and VUS

Complexity of data analysis: equitable access and reimbursement feasible for everyone

Proper classification of variants (clinically valid and actionable, clinically valid but not directly actionable, or of unknown significance) and constant updating of this knowledgeb

Data management (IT) in the laboratory (data tracking, handling and storage; and quality control)c

Data management (physicians) in the clinic (lack of background genetics education and training to properly manage and report genomic results)

Lack of consensus on data return (what results must be generated, returned to the physician and the patient, and to what extent and how the return of unfavourable or potentially harmful results should be prevented)

Genomic data availability and accessibility in medical records and databases (privacy and confidentiality)

Definition of the need to recontact periodically to reassess significance of novel variants and VUS

Genetic counselling: increase in the amount of time needed and training of professionals on communication strategies with patients and families

^aAlso called secondary, unsolicited, unexpected or unanticipated variants

^bEuroGentest has published recommendations on NGS where variants are classified in different categories: “It is recommend the use of a variant classification into these 5 levels, namely: pathogenic (5), likely pathogenic (4), unclassified UVs (3), likely benign (2) and benign (1) variants.” (Eurogentest—Guidelines for Diagnostic Next Generation Sequencing 2015 [in press])

^cWGS is expected to reveal three to four million variants, WES is expected to reveal about 20,000 variants (Johansen Taber et al. 2014)