When a patient has a suspected rare or genetic condition, timing is everything. Moving from clinical uncertainty to a definitive answer can fundamentally shift care plans, prevent "diagnostic odysseys" and unnecessary testing, and provide families with much-needed clarity.
Today, leading medical organizations—including the American College of Medical Genetics and Genomics (ACMG)1, the American Academy of Pediatrics (AAP)2, and the National Society of Genetic Counselors (NSGC)3—recommend exome and genome sequencing early in the diagnostic journey for many clinical presentations. But for some providers, choosing the right path can feel complex.
Traditionally, providers relied on single- or multi-gene panels or chromosomal microarrays (CMA) as a first step. While useful, these strategies can often miss the underlying cause of complex conditions, as they are limited to analyzing a small portion of a person’s genetic material. Both genome and exome sequencing have demonstrated higher diagnostic yields for complex presentations like intellectual disability/developmental delay (ID/DD) and epilepsy1,4-6—making them more likely to lead to a clear diagnosis.
The key difference between the two is scope:
According to leading medical organizations1-3, if your patient presents with any of the following, exome or genome sequencing should be considered as a first-line test:
Sequencing can also help diagnose rare or unexplained conditions associated with:
Comprehensive exome or genome sequencing can be especially valuable when a patient has already been evaluated by multiple specialists, had a previous negative genetic test, or when their healthcare provider has concern about a possible genetic disorder, metabolic condition, or mitochondrial disease. In these cases, exome or genome sequencing can provide a broader view to help identify (or rule out) known genetic causes.
In general, genome sequencing is the most comprehensive option and typically offers the highest diagnostic yield. However, practical factors such as insurance coverage can often be the deciding factor—some state Medicaid programs and commercial plans are more likely to cover exome sequencing than genome sequencing.
If genome sequencing isn’t covered under your patient’s plan, exome sequencing is often the best place to start to move the diagnostic process forward quickly. And if exome results are negative or inconclusive, genome sequencing can be ordered next for a more complete analysis.
Most laboratories treat Exome and Genome as two entirely different workflows. MyOme makes it easier to choose between exome and genome testing by running both tests on a whole-genome backbone, even when an exome is ordered. This delivers three key benefits: (1) stronger exome performance and (2) built-in features to boost detection, and (3) simplified reflex workflows.
The Bottom Line
If a patient has developmental delay, intellectual disability, congenital anomalies, epilepsy, or other unexplained neurologic or systemic findings, exome and genome testing should be considered early for an efficient path to answers.
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