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A Systematic Approach to the Reporting of Medically Relevant Findings From Whole Genome Sequencing

Heather M McLaughlin et al. BMC Med Genet. .
Free PMC article


Background: The MedSeq Project is a randomized clinical trial developing approaches to assess the impact of integrating genome sequencing into clinical medicine. To facilitate the return of results of potential medical relevance to physicians and patients participating in the MedSeq Project, we sought to develop a reporting approach for the effective communication of such findings.

Methods: Genome sequencing was performed on the Illumina HiSeq platform. Variants were filtered, interpreted, and validated according to methods developed by the Laboratory for Molecular Medicine and consistent with current professional guidelines. The GeneInsight software suite, which is integrated with the Partners HealthCare electronic health record, was used for variant curation, report drafting, and delivery.

Results: We developed a concise 5-6 page Genome Report (GR) featuring a single-page summary of results of potential medical relevance with additional pages containing structured variant, gene, and disease information along with supporting evidence for reported variants and brief descriptions of associated diseases and clinical implications. The GR is formatted to provide a succinct summary of genomic findings, enabling physicians to take appropriate steps for disease diagnosis, prevention, and management in their patients.

Conclusions: Our experience highlights important considerations for the reporting of results of potential medical relevance and provides a framework for interpretation and reporting practices in clinical genome sequencing.


Figure 1
Figure 1
MedSeq Project variant analysis workflow. M (million), Genome Report (GR), variant of uncertain significance (VUS).
Figure 2
Figure 2
Variant classifications from 20 genomes (a). A total of 381 unique variants were assessed and classified after filtration (b) HGMD classification comparison. Disease causing mutation (DM), likely disease causing mutation (DM?), loss-of-function (LOF).
Figure 3
Figure 3
Example Genome Report result summary.

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