Understanding Genetic Testing: What Every Rare Disease Family Should Know
Genetic testing has transformed rare disease diagnosis. Here is a plain-language guide to common tests, what results mean, and how to use them to advocate.
Whole exome sequencing
Whole exome sequencing (WES) reads the protein-coding portion of your genome, roughly 1-2% of the total DNA, where most disease-causing variants live. It is often the first deep test ordered when a clinical diagnosis is unclear.
Whole genome sequencing
Whole genome sequencing (WGS) reads everything, including the non-coding regions and structural variants WES can miss. WGS is becoming more available and is increasingly the first-line test in many academic centers.
Variants of uncertain significance
A variant of uncertain significance (VUS) is a real DNA change that we cannot yet classify as harmful or benign. A VUS is not a diagnosis and should not drive treatment. Re-analysis every 1-2 years often reclassifies these as more data becomes available.
De novo mutations
De novo means new: a change that arose in your child and is not inherited from either parent. De novo variants are a common cause of rare pediatric disease and do not reflect anything either parent did or did not do.
Genetic counseling
A genetic counselor translates results into a real-world plan. They explain inheritance, recurrence risk, family implications, and the limits of what a result can tell you. Ask for a counselor before testing, not only after.
Interpreting results
Read the report alongside someone trained to interpret it. Watch the date: science moves quickly and a 2018 result deserves a 2026 re-analysis. Keep the lab report itself in your records, not only the clinician's summary.
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About the author
Forgotten Rare Team writes alongside caregivers, clinicians, and rare disease families. Our articles are reviewed for clarity and warmth, never for noise.
