DNA Methylation Signature Testing
Epigenetic alterations are observed in many congenital disorders, particularly neurodevelopmental disorders. For variants in genes encoding or impacting epigenetic regulators and associated with the clinical findings, DNA methylation is assessed to guide interpretation of potential pathogenicity. This approach focuses on genes with well-established epigenetic signatures and for which the presence of a unique signature can indicate the presence of a pathogenic variant and thereby, reclassify a VUS.
Turnaround time is 4 weeks.
Who is this test for?
- Patients for whom assessing DNA methylation would be useful to confirm the pathogenicity of a VUS
- Patients with a clinical presentation suggestive of a possible underlying epigenetic disorder
- Research study samples
Sequencing & Interpretation
Prior to performing DNA methylation studies, clinical Sanger sequencing will be done on the reported VUS to confirm its presence and to allow its reclassification following completion of the DNA methylation analysis. Sanger validation will not be done on research samples.
Alamya Health utilizes the Illumina® Infinium Human Methylation EPIC BeadChip v2.0 platform. This platform contains 935,000 CpG sites for detection of DNA methylation at single CpG resolution. DNA methylation profiles are compared to reference disease gene and control profiles in order to classify variants. Principal component analysis is used to visualize the profile of the test sample in comparison to the distinct profiles of controls and individuals with pathogenic variants in the disease gene. Data will be analyzed for established DNA methylation signature(s) relevant to the reported VUS and/or the clinical presentation.
Test Limitations
The absence of a detectable DNA methylation signature does not rule out variant pathogenicity. Uncertain results may result from factors such as mosaicism, cell type, a variant with reduced expressivity etc.
Samples & Ordering
Requirements
- 1 tube (3.0ml-5.0mL; min 1.0ml) of whole blood drawn in an EDTA tube
- This tube/kit can be ordered through our kit order page
- Samples should be shipped at ambient temperature (18-25℃) or refrigerated (2-8℃).
- Whole blood is stable for 5 days at ambient temperature (18-25℃) or 7 days refrigerated (2-8℃). Do not freeze.
Shipping Address
Alamya Health
℅ Breakthrough Genomics
2 Hughes, #100
Irvine, CA 92618