Variant reporting is an evolving theme in the context of genomic medicine. Variant reporting is where all the bioinformatics and computational genomics are finally going to be visible at the point of care. Style and visual elements in variant reporting may vary between organizations and regulated by country-specific law related to genetics and genomics. There are multiple reporting strategies discussed by independent researchers and consortiums for variant interpretation (for example: see McArthur et.al and Shameer et.al) and reporting. However, I would recommend discussing with your clinician/genetic counseling team for the local consensus.
The report has three primary end-users(recipients): genetic counselor, care provider, and patient. Balancing the three arms are imperative in the context of precision. Dynamic reporting for different groups with various levels of information is another strategy, but often need more resource, dedicated curation team, etc. These reports are bound to have different impressions for patients from different cultural backgrounds and socio-economic regions - we should be inclusive and think of it as a team effort than just creating an output file.
If you are delivering the results with the help of a genetic counselor, your report should adhere to American College of Medical Genetics ACMG and Association for Molecular Pathology (AMP) guidelines (in the United States). Here is a link to their recent official report. They provide examples, tools, and strategies to make report concise yet accessible to all three types of recipients. These guidelines are to change periodically; variant-associations can also evolve over time - please ensure you have iterative mechanisms to re-annotate and provide the latest report at the point-of-care during patient visits.
For example:
- Criteria for classifying pathogenic variants
- Criteria for classifying benign variants
- Rules for combining criteria to classify sequence variants
As per the consensus: A variant of uncertain significance should not be used in clinical decision making. The rationale here is, if we don't know the biological or clinical effect, reporting the variant to physicians or patients is not beneficial.
Providing literature support or other evidence could be based on resources available in your hospital/health system. I have integrated genetic variant reports with resources like GHR, OMIM, MedlinePlus to describe clinical phenotypes. For literature reference, we have often cited the latest paper with largest sample size and replication in >2 studies. I would recommend to keep the literature section current and minimal with direct links to PubMed or PubMed Central. You can also integrate custom (Ask Mayo Expert) or commercial healthcare information resource (UpToDate) as part of your reports. Please ensure that your recipients have access to such information and the link-outs are certified by hon-code or other healthcare information reliability indicators.
If you need some inspiration, please take a look at the report we have created for MI-GENES clinical genomics trial. If you adopt this model, please feel free to cite our work.
I am assuming you are doing this as germline testing? The answers below assume this but there would be different answers if you were looking for somatic mutations in tumour testing for instance. So it would be good to be clear about the context you are doing clinical genomics in.