Disclaimer: This Points to Consider document is designed as an educational resource to provide best practices for medical genetic clinicians, laboratories, and journals regarding the provision, publication, and dissemination of patient phenotypes in the context of genomic testing, clinical genetic practice, and research. While the goal of the document is the improvement of patient care, the considerations and practices described should not be considered inclusive of all proper considerations and practices or exclusive of others that are reasonably directed to obtaining the same goal. In determining the value of any practice, clinicians, laboratories, and journals should apply their own professional standards and judgment to the specific circumstances presented.
The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the authors' affiliated institutions.
As comprehensive genetic and genomic testing are increasingly incorporated into the care of patients, there is a critical need for heightened consideration of professional responsibilities and implications in the provision and publication of patient phenotypic information. We offer a best-practice perspective focused on the best interest of the patient and recognition of the roles of laboratories, clinicians, and journals toward this endeavor. This Points to Consider document expands on the American College of Medical Genetics and Genomics’ recent position statements on genomic data sharing1 and standards for the interpretation of sequence variants.2 Each document emphasizes how vital it is for the richest possible clinical and genetic data to be made available in the clinical care process and wider medical and scientific communities to facilitate broad success in reaching a clinical diagnosis, best-possible variant interpretation, and well-curated literature and databases. The following framework represents key best-practice responsibilities applied to professionals involved in the provision and publication of phenotypic and genotypic information grounded on the ethical construct of beneficence and the premise that ensuring optimal data sharing is the gold standard among clinicians, diagnostic laboratories, and researchers.
Provision of clinical data during testing
The current model of genetic and genomic testing assumes the laboratory has access to clinical data sufficient to prioritize variants for analysis and accurately interpret variants during clinical reporting. Certain types of conditions and phenotypes that prompt genetic testing are amenable to formulaic reporting on requisition forms. For example, in suspected cancer predisposition syndromes it is simple to provide types of cancer in an individual and their relatives. However, in other situations (e.g., syndromic presentations) phenotypes can be quite complex and varied, making it more difficult to communicate pertinent phenotypic data. In these areas, where “open text” fields on a requisition form may be necessary for communication of phenotypic features to the laboratory, it will be particularly important, yet potentially challenging, for clinicians to take adequate time and thought to include the most pertinent phenotypic findings. We recognize this ideal may be difficult to realize given limited resources, including time and staff, and that viable alternatives in the future may involve structured phenotype entry into the electronic health record with single-push forwarding to laboratories as well as less clinical correlation by laboratories and more by ordering clinicians.
The following are best practices:
Clinicians should provide detailed phenotypic and family history data to clinical laboratories, including phenotypic features the clinician may not initially see as relevant, appreciating the potential for laboratories to find unsuspected etiologies or multiple causes for independent clinical findings. Attaching the clinic note and family history table or pedigree (stripped of nonproband protected health information) may be considered sufficient for this purpose. If the ordering clinician receives a request from the laboratory to provide additional information (subsequent bullet), reasonable effort should be made to provide the requested information.
Clinical laboratories should ensure that clinical information is considered in the interpretation of genetic and genomic findings related to the test indication. Laboratories should request these data up front, but if insufficient clinical information is supplied to adequately interpret findings, additional information necessary to interpret the genetic data should be requested.
The clinician and laboratory should try to discuss and identify further studies that may improve the interpretation, potentially as an iterative exchange in response to genotypic information generated by clinical laboratories, with the clinician sharing multiple rounds of information possibly including physical examination, laboratory studies, imaging, and family history, when feasible. However, additional studies should not delay a laboratory report.
Given the utility of segregation, de novo, and allelic (cis/trans configurations) evidence in the evaluation of variant pathogenicity, informative family member samples should also be requested when needed to clarify variants of uncertain significance that have a high prior probability of being causative for the indication for testing. If family member samples are sent, genotype–phenotype correlation should be performed to ensure consistency with proband variant interpretation.
Clinical laboratories should also provide clinicians with access to knowledgeable staff members of the laboratory (genetic counselors, laboratory directors, etc.) capable of discussing results, variant evidence, genotype–phenotype correlations, and how the provision of phenotypic data will inform the interpretation of variants.
H.L.R. and C.L.M. were supported in part by National Institutes of Health HG006834.
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Notes regarding ICMJE guidelines
3Excerpt: “The ICMJE [International Committee of Medical Journal Editors] recommends that authorship be based on the following 4 criteria: Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND Drafting the work or revising it critically for important intellectual content; AND Final approval of the version to be published; AND Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved).”
4Clinical information on a patient is considered research by the ICMJE—even if not subject to institutional review board review—once published or publicly disseminated. Excerpt: “Patients have a right to privacy that should not be violated without informed consent….Informed consent should be obtained if there is any doubt that anonymity can be maintained.”