Genome interpretation: Clinical correlation is recommended

In a brain MRI report, the following words often appear: “clinical clinicians, this would represent a need to submit more information correlation is recommended”. These words signify that inadequate clinical informationwas provided, or that an unexpectedfinding on theMRI should be assessed clinically. “Clinical correlation is recommended” is less common in a report about a single gene or simple gene panel. This is because the very act of ordering the test conveys much of what is important about the clinical situation, and only rarely is further information needed. Genetics labs are moving into new territory as they adopt nextgeneration genomic sequencing. When moving beyond single gene tests and simple panels, more clinical correlation is needed. The complexity of interpretation becomes similar to a brain MRI, only more so. In an exome, thousands of variants are found. Even after comparing to other family members, and using estimates of variant pathogenicity, many genes must be considered. Sometimes clinical correlation can be as simple as using the key clinical finding, assuming that you know which finding is key. But sometimes the situation is more complicated: variants are found in a gene that hadn't been considered clinically, or two genes are needed to explain the clinical picture, and more clinical correlation is needed. For brain MRI scans, this clinical correlation is institutionalized as neuroradiology rounds held several times a week by many neurology inpatient services. How should the analogous clinical correlation for genomic interpretation be structured? The core principle of clinical correlation should be that detailed information about the patient's findings, the phenotype, is combined with detailed information in the annotated variant table, the genotype. Since this is done in the wider context of considering all known phenotypes, the result is a “genome–phenome” analysis. In what venue should the “aha” of this clinical correlation occur? Each venue has plusses and minuses: