How to read and make sense of the genetic testing results your family received.
After receiving a genetic diagnosis, many families want to understand more about what the test found. This page explains the key terms on a genetic test report and introduces the databases where researchers track information about SETD5 variants. You do not need to understand all of this. But if you are someone who feels better with more information, this page is for you.
Interactive guide
Click any row to see what it means in plain language. Fields with multiple possible values show all the options your report might contain.
This is the gene where the lab found a change. SETD5 provides instructions for making a protein involved in brain development and gene regulation. It sits on chromosome 3 at position 3p25.3. Changes in this gene are associated with intellectual disability and developmental delays - a condition sometimes called SETD5 Syndrome or MRD23.
This is the exact "address" of the change in the DNA. The c. notation tells the lab where in the gene the change occurred. The p. notation describes how the protein is affected. You do not need to memorize this - but it's the key identifier when talking to a genetic counselor or searching databases like ClinVar.
This describes what kind of change happened to the DNA. Different types of changes affect the gene in different ways. Your report will list one of the following:
This is the lab's assessment of whether this change is responsible for your child's condition. Labs use a five-tier system defined by the ACMG (American College of Medical Genetics):
This tells you where the change came from and how it's passed through families. Most SETD5 cases are de novo, but not all reports will say this - it depends on whether parental testing was done.
This describes how many copies of the gene are affected. You have two copies of most genes - one from each parent.
These are the specific evidence codes the lab used to arrive at the classification above. Each code represents one piece of evidence. You don't need to understand these - they're primarily for clinicians and genetic counselors. But if you're curious:
This is a sample report for educational purposes only. It does not represent any individual's actual genetic test results.
Interpreting your results
This genetic change is known to cause SETD5 Syndrome. There is strong evidence from multiple sources. This is the clearest result.
Strong evidence that this change causes SETD5 Syndrome, but hasn't been seen in as many people yet. Many clinicians treat a likely pathogenic result similarly to a pathogenic one, but your genetics team will guide how this applies to your child's specific situation.
The lab found a change in SETD5, but there isn't enough evidence yet to say whether it causes the condition or is harmless. A VUS doesn't confirm a diagnosis, but it doesn't rule one out either. It means more information is needed. Classifications can and do change over time as research grows.
This change is probably or definitely harmless. Common in the general population and not thought to cause disease.
Some families find the following approaches helpful in working with their genetics team over time: parental testing (to see if either parent carries the same change); enrolling in research registries, which helps researchers gather data — see the Research Registries guide for options open to SETD5-related disorder families; and asking the lab whether reclassification may be possible as new evidence becomes available. Your genetic counselor can advise on what makes sense for your situation.
What happened in the DNA
One letter in the genetic code changed, which changes one building block of the protein. The protein is still made but may not work correctly. Like a typo that changes the meaning of a word.
One letter changed in a way that creates a premature stop signal. The protein gets cut short and usually cannot do its job. Like a sentence that stops in the middle.
A letter was added or deleted, throwing off the reading of everything that follows. The genetic code is read in groups of three, so shifting by one scrambles all the instructions that come after it.
A piece of the genetic code is missing. Can be small (a few letters) or large (a section of chromosome). Larger deletions involving neighboring genes alongside SETD5 may cause additional features.
A section of genetic code is copied, appearing twice instead of once.
The type of variant your child has can sometimes give clues about severity, but it is not a reliable predictor. Two people with the exact same variant can look very different. Researchers are still working to understand why.
Variable expression
Variable expressivity describes the fact that the same genetic change can cause a wide range of outcomes. Two people in the same family with the identical SETD5 variant can have very different experiences — one might have relatively mild learning differences, while another has more significant support needs across multiple areas.
Genetic background plays a major role. Each person carries roughly 20,000 genes that all interact with one another. These other genes (sometimes called "modifier genes") can influence how SETD5 Syndrome shows up — which is part of why no two children look exactly alike. Your child's unique combination of genes from both parents shapes their outcome in ways researchers are still working to understand.
Variant type and location matter, but not in a simple way. Where in the SETD5 gene the change occurs can affect how much protein is made and how it functions. But the relationship between variant location and severity is not yet well-understood. This is an active area of research.
Where the research lives
These are the databases researchers, genetic counselors, and clinicians use. You do not need to use them. But if you want to look up your child's specific variant, here is what each one does.
Support available
At the time this page was last updated, families enrolled in Simons Searchlight could access free genetic counseling. Many families find this to be a helpful resource. A genetic counselor can walk you through your child's specific report and answer questions that no website can. Check the Simons Searchlight website for current availability.
Want a broader overview? For a comprehensive look at what SETD5 Syndrome is and how it affects development, see our Understanding SETD5 Syndrome page.