> For the complete documentation index, see [llms.txt](https://docs.omics.ai/products/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://docs.omics.ai/products/workbench/variant-interpreter/reviewing-variants/methylation-imprinting.md). # Methylation & imprinting Long-read sequencing reads DNA methylation directly from the same data used for variant calling, with no separate assay. Because reads are phased, methylation can be assigned to each parental copy, which is what makes imprinting analysis possible. Imprinting is when a gene is normally expressed from only one parental copy. Loss of imprinting, the expected pattern being disrupted, underlies several imprinting disorders. The **Methylation** tab lists the sample's methylation calls over imprinted, differentially methylated regions, so you can find regions whose methylation departs from what you'd expect. {% hint style="info" %} The **Methylation** tab appears only when the case includes methylation results for the sample. {% endhint %} ## The methylation table Each row is one region. The default columns include **Locus**, **Overlapping Genes**, the region's coordinates, **Mean Coverage**, **Mean Mod Score** (the primary methylation measure, from 0 to 100), **Source**, **Cytogenetic Band**, **CpGs Observed**, **Pooled Meth %**, **Fraction Sites Meth**, and **Meth Threshold**. Rows are sorted by chromosome, then start position. **Source** tells you which reads the values come from: **Combined** (both haplotypes together), **Haplotype 1**, or **Haplotype 2**. ## Filters The filter drawer offers **Mean Mod Score**, **Source**, **Mean Coverage**, **CpGs Observed**, **Chromosome**, and **Start Position**. The tab opens pre-filtered to regions with a **Mean Mod Score** of 15 or below, or 85 or above, from the **Combined** source. These are the strongly hypomethylated and hypermethylated regions. Clear or widen these filters to see every region. ## How methylation findings are flagged A region is flagged when its combined mean modification score is **15 or below** (**Hypomethylated**) or **85 or above** (**Hypermethylated**). These regions appear as priority findings on the [Summary tab](/products/workbench/variant-interpreter/getting-started/the-summary-tab.md), in the Weak evidence tier, marked as hypomethylated or hypermethylated. {% hint style="warning" %} Flagging uses a fixed cutoff, not a comparison with a population reference range for each region. No expected range per locus is loaded, so the detail view can't show one. Judge whether a flagged region is abnormal for its locus from your own knowledge of the expected imprinting pattern. {% endhint %} ## The region detail Opening a region shows the **Variant Summary**, **Region composition**, and **Methylation** cards. A **Not available for this variant type** card lists the evidence methylation calls don't carry yet: * **Expected methylation range**: no expected range per locus is ingested. * **Per-allele split**: in the detail view, methylation is pooled across both haplotypes. To compare haplotypes, use the **Source** filter in the table. * **Clinical evidence**: there's no disease annotation for imprinted loci. * **Predicted effect**: there's no automated classification of methylation calls. The **Browser** tab opens a family view with each available member's haplotype-tagged reads. See [The genome browser (IGV)](/products/workbench/variant-interpreter/reviewing-variants/genome-browser.md). ## How to review 1. Start from the default view of flagged regions. 2. For each region, compare the **Haplotype 1** and **Haplotype 2** rows with the **Combined** row. At a normally imprinted region, one haplotype is typically methylated and the other isn't; a region methylated on both copies, or neither, suggests loss of imprinting. 3. Check **Mean Coverage** and **CpGs Observed** to make sure the region is well covered. 4. Flag regions showing loss of imprinting or otherwise unexpected methylation, and [classify](/products/workbench/variant-interpreter/classifying-variants.md) them so they can be included in the [report](/products/workbench/variant-interpreter/generating-a-report.md). --- # Agent Instructions This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. Learn more at gitbook.com. ## Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation by asking a question. Perform an HTTP GET request on the following URL with the `ask` and `goal` query parameters: ``` GET https://docs.omics.ai/products/workbench/variant-interpreter/reviewing-variants/methylation-imprinting.md?ask=&goal= ``` `ask` is the immediate question: it should be specific, self-contained, and written in natural language. `goal` is what the user is ultimately trying to achieve, the reason they need the answer. Sharing it helps GitBook give you a better, more relevant answer. A goal is most helpful when it describes the outcome the user wants rather than restating the question. For example, with `ask=how do I create an API token`, a goal like `automate deployments from our CI pipeline` lets GitBook tailor the answer to that use case. The response will contain a direct answer to the question and relevant excerpts and sources from the documentation. Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.