GEBRA Use Guide: Symptom-driven Update — When Phenotypes Evolve, Your Shortlist Should Too

“My patient’s symptoms changed.”

Familiar story: an infant first presents with developmental delay and hypotonia. Months later, the echo shows dilated cardiomyopathy. In traditional pipelines, that means kicking off a new request, re-uploading a VCF, re-filtering, and waiting—while treatment decisions pause.

Symptom-driven Update was built to remove that lag. Update the phenotype; GEBRA updates the variant ranking—automatically.

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What it does

1. Edit symptoms (HPO) on the sample page (✏️ icon).
   
2. Save.
   
3. 3ASC immediately reprioritizes variants based on the updated phenotype. No new upload. No manual rebuild of filters. Results refresh in seconds—right in your 3ASC view.
   

Why it matters: Diagnosis is a moving target. As the phenotype clarifies, your shortlist should, too.

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A concrete example of symptom-based update

1. Initial phenotype: developmental delay + hypotonia → WDR45 prioritized; PEX6 around rank 5.

2. Add new symptom: dilated cardiomyopathy.

3. Effect: TTN rises in priority due to phenotype–gene association; the shortlist updates instantly for review.

This is not a new end-to-end run; it’s a phenotype-aware reprioritization that brings the most plausible candidates to the top—fast.

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The updates you get with one click

When HPO changes, GEBRA recalculates:

• Phenotype–genotype matching (HPO-based)
• Inheritance consistency with the clinical picture
• ACMG/AMP evidence scoring refresh
• False-positive risk signals (e.g., artifact-prone regions)
  You get a refreshed, evidence-backed order of candidates while retaining full explainability for boards and reports.

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Workflow impact

Step	Before	With Symptom-driven Update
Add/modify symptoms	New analysis request	Inline update on the sample
Get updated shortlist	Queue + wait days	Seconds, inside 3ASC
Cost	Often additional reanalysis fee	Free within the same sample
Explainability	Manual cross-checks	Evidence refreshed alongside rank order

Result: faster feedback to patients, fewer administrative loops, and an interpretation that keeps pace with the case.

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When to use it?

• New clinical features emerge (e.g., seizures, cardiomyopathy, neuropathy).
• Atypical presentations where the initial shortlist doesn’t fully explain the phenotype.
• Follow-up visits where longitudinal data sharpen the clinical picture.
  

If 3ASC gives you speed, Symptom-driven Update gives you timing—keeping the ranking current each time the phenotype evolves.

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It only takes seconds to get started

1. Open the sample → click ✏️ Edit symptoms.
2. Search/add/remove HPO terms → Save.
3. Review the updated High/Mid tiers in 3ASC and proceed to evidence review or reporting.

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Pair it with these GEBRA tools 🛠️

• 3ASC: AI-powered prioritization you can trust for a fast, transparent shortlist. (Take a look at 👉 the ‘GEBRA Use Guide : 3ASC.’)
  
• Filters: If the updated shortlist still feels incomplete, dive into VUS with targeted filters.
  
• Knowledge Base: Leverage prior cases (VariantsDB/ReportedDB) to see how similar variants behaved across your cohort.
  
• Gene Coverage: Confirm that critical genes were adequately covered before calling a confident negative.

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Learn More

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