The introduction of the innovative PanelApp by Genomics England has revolutionised the approach to the development of its diagnostic grade gene panels. By encouraging wide scale engagement with the clinical and research community to provide input to the development of their panels, this should maximise the utility of all the work and knowledge that is available.
Bridging the evidence gap
In support of this initiative, Genomics England has drafted targeted gene panels based on a systematic method of reviewing established panels from four sources. It is now seeking review and feedback on these panels from the clinical and scientific community. This approach should ensure that the maximum possible information is available to decide on the final panels to be tested and also provide an on-going process to update and improve the gene panels going forw ard. This is critical as there remains in general significant evidence gaps and also increasing evidence for the genotype-phenotype relationships for many conditions/phenotypes.
Concerns over testing variability
The development of gene panels over the last few years has resulted in variation in the tests offered for the same condition/phenotype, in terms of what genes have been included in their design and therefore tested for. This has raised concerns in the clinical community about the potential unacceptable variability in test performance. In turn the clinical scientific community has attempted to address this in the absence of consensus standards for the evidence framework to assess genes for the inclusion in panels.
Leading the way
Genomics England has shown leadership in addressing this challenge through the development of their evidence framework for deciding on the necessary evidence for inclusion in diagnostic gene panels. The framework has been developed building on the experience and results of the ClinGen and Deciphering Developmental Disorders Genotype-Phenotype Database initiatives. This is an important step in moving to an international approach in the development and use of standards to be applied to assessing evidence for the development of diagnostic grade gene panels. This should improve the quality and safety of diagnostic gene panel testing for patients.
The Genomics England Clinical Interpretation Partnership (GeCIP) Validation & Feedback domain has a central role in the development of the diagnostic grade gene panels and the interpretation and reporting of the results. It will be particularly important that this GeCIP has adequate resources to perform these wide ranging roles which are so central to achieving the desired outcomes from this project.
The outstanding challenge of clinical translation
Whilst the field of genomics continues to develop exponentially, the challenge of translating this progress into clinical care remains. Many issues still need to be addressed and the Foundation has highlighted some of these through its clinical genome analysis programme including – the necessary improvement in the quality of the evidence base, minimum standards for sequence generation and better data sharing for improved clinical diagnosis. The Genomics England initiative is therefore to be welcomed and supported.
To find out how experts use and share phenotype information, see our latest briefing, Phenotyping patients for genomic diagnostics.