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This issue of the _European Journal of Human Genetics_ presents, on behalf of EuroGentest and the European Society of Human Genetics (ESHG), guidelines for the evaluation and validation of
next-generation sequencing (NGS) applications for the diagnosis of genetic disorders.1 They address a wide spectrum of points to consider, including a definition of the diagnostic utility of
an NGS test, a ranking of NGS assays on the basis of essential _vs_ optional genes they might include, standardization of quality parameters, policies for dealing with the additional
features that are intrinsic to NGS testing, such as secondary and unsolicited findings, and distinctions to be made depending on the research _vs_ diagnostic setting. The guidelines stress
the necessity for frequent updating in this rapidly evolving field. These guidelines propose that groups of clinical and laboratory experts should define ‘core gene lists’ that must be
analysed in any particular diagnostic or research approach _vs_ additional genes that might be added, but cannot be considered as mandatory, mainly because of their low diagnostic yield.
Selecting these core genes is not trivial, because even the definition of a core gene is still under debate. Evidently, the frequency of mutations in the gene in relation to the phenotype is
an important parameter. But it is not easy to define the threshold: can a gene that explains less than 1% of the cases be a core gene? Probably not, but practitioners like to have the
largest possible yield when ordering a test. At the same time, NGS is appealing as one can easily increase the number of genes in a diagnostic panel. Shall a core gene be completely
sequenced, and shall a core gene panel be a ‘type A’ test, as defined in the diagnostic NGS guidelines?1 Yes if it is about warranting maximal sensitivity, no if it is about filling up—using
Sanger sequencing for instance—gaps in the sequence in exons (or functional domains of the protein) in which no one has ever detected mutations, even in large cohorts. Thus, it is not
decided yet whether we are developing ‘core gene lists’ or ‘core exon lists’. But irrespective of that discussion, it is time for people to get together and publish core gene/exon lists, and
harmonize the diagnostic offer for the sake of the patients. As a prototype for such a group consensus paper this issue also publishes the first NGS-adapted Clinical Utility Gene Card for
Hereditary Thoracic Aortic Aneurysm and Dissection (TAAD).2 We hope that the scientific and clinical community will find it useful to find a specific example for one of the recommendations
of the EuroGentest/ESHG NGS guideline, and that it might inspire the readership for further consensus papers of this kind, and for reading and applying the diagnostic NGS guidelines.
REFERENCES * Matthijs G, Souche E, Alders M _et al_: Guidelines for diagnostic next generation sequencing. _Eur J Hum Genet_ 2016; 24: 2–5. Article CAS Google Scholar * Arslan-Kirchner M,
Arbustini E, Boileau C _et al_: Clinical utility gene card for: Hereditary Thoracic Aortic Aneurysm and Dissection (TAAD) Including Next Generation Sequencing Based Approaches. _Eur J Hum
Genet_ 2016; 24: 146. Article CAS Google Scholar Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Human Genetics, Centre for Human Genetics, KU Leuven,
Leuven, Belgium Gert Matthijs * Institute of Human Genetics, Hannover Medical School, Hannover, Germany Anna Dierking & Jörg Schmidtke Authors * Gert Matthijs View author publications
You can also search for this author inPubMed Google Scholar * Anna Dierking View author publications You can also search for this author inPubMed Google Scholar * Jörg Schmidtke View author
publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Gert Matthijs. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no
conflict of interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Matthijs, G., Dierking, A. & Schmidtke, J. New EuroGentest/ESHG guidelines and
a new clinical utility gene card format for NGS-based testing. _Eur J Hum Genet_ 24, 1 (2016). https://doi.org/10.1038/ejhg.2015.229 Download citation * Published: 28 October 2015 * Issue
Date: January 2016 * DOI: https://doi.org/10.1038/ejhg.2015.229 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a
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