Rough draft.This research track is under review with Dr. Atit's lab. Content and sequence may still change.

Here's an example of what's due today

Looking Up a Variant

Genetics domain · Lesson 6 of 20 · Medical Interventions (MI), with PBS overlap

Today's goal: Students will navigate ClinVar and OMIM and classify a variant entry as benign, pathogenic, or a variant of uncertain significance (VUS).

Learn first

What a finished product looks like

This is a model of the work you should turn in. Use it to check your own: match the structure and the level of detail, do not copy it. Your wording should be your own.

Variant classification note

Completes: A one-line ClinVar-style classification of a new variant plus the next-evidence request.

Classification note: A brand-new IRF6 change reported in no database is a variant of uncertain significance (VUS) at this moment, because there is no frequency data, no family-segregation data, and no prior reports to weigh.

Most valuable next evidence: segregation data, whether affected relatives carry the change and unaffected relatives do not. If the change repeatedly appears in affected family members and is absent from healthy ones across several families, the call could move from VUS toward pathogenic.

Also due today: State the one next piece of evidence (segregation) most likely to move the call.

Check yourself

Worked Claim, Evidence, Reasoning (from the database)

Here is the whole reasoning move done once, on the same kind of evidence you will pull from the tool. Read how the claim, the actual value from the database, and the reasoning fit together, then write your own the same way.

Evidence from gnomAD (Genome Aggregation Database)Open the tool

The question: A lab finds the IRF6 change R84C in Mateo. Is this change rare enough in healthy people to support calling it harmful?

C
Claim. The IRF6 R84C variant is consistent with being pathogenic, not a harmless common variant.
E
Evidence (what the tool actually showed). gnomAD, IRF6 R84C: global allele frequency 0 (it appears in 0 of ~140,000 healthy individuals); IRF6 gene constraint shows loss of function is not tolerated (high pLI, low LOEUF).
R
Reasoning (from the result to the inference). A change that damages a known disease gene yet is completely absent from a large healthy population is exactly the pattern expected for a disease-causing variant; if R84C were harmless, we would expect to see it at least occasionally in healthy people. Its absence in gnomAD, combined with IRF6 being intolerant to loss of function, adds weight toward pathogenic. (gnomAD does not make the call by itself; here it lines up with ClinVar, which already lists R84C as pathogenic in many PPS families.)

Now write your own. Look up your variant or gene, read the value, then go result inference, just like this.

Learn first

How this was built, step by step

The finished product above did not appear all at once. Here is the path from the question to the turned-in work, so you can follow the same steps.

1Look the variant up in ClinVar and check for any prior report or clinical-significance call.
2Check its frequency in healthy people using gnomAD; a damaging change absent from gnomAD is a red flag, while a common one points to benign.
3If there is no ClinVar report, no family data, and no informative gnomAD frequency, you cannot call it benign or pathogenic.
4Record it as a for now.
5Name the single most useful next evidence: testing relatives to see whether the change tracks with the (segregation).
6Check it against the rubric, then submit.

How this is graded (rubric)

For: Given a patient's IRF6 change reported in no database, write the call you would record right now using the three categories and name the one piece of evidence you would most want next to move it off uncertain.

Criterion	Proficient	Developing	Beginning
Complete	Every required part of the artifact is present and filled in.	Most parts are present, but one is missing or left blank.	Several parts are missing.
Accurate	The science and data are correct and match the evidence.	Mostly correct, with a small factual slip.	Key science or data is wrong.
Scientific reasoning (CER)	States a claim, backs it with specific evidence, and explains the reasoning.	Has a claim and evidence, but the reasoning is thin or missing.	Gives an answer with no evidence or reasoning.
Professional communication	Clear, organized, and labeled the way a clinician or scientist would write it.	Readable but disorganized or missing labels.	Hard to follow.
Submitted	Turned in the right way (Schoology for routine work) and confirmed.	Turned in, but in the wrong place or unconfirmed.	Not turned in.

How the model answer scores against this rubric

CompleteProficient: Nothing is left blank: the model fills every part of "Given a patient's IRF6 change reported in no database, write the call you would record right now using the three categories and name the one piece of evidence you would most want next to move it off uncertain.".
AccurateProficient: Every number and claim matches the case evidence.
Scientific reasoning (CER)Proficient: It names a claim, cites the specific evidence, and explains the reasoning, not just the answer.
Professional communicationProficient: It is organized and labeled like a real chart note.
SubmittedProficient: It would be turned in on Schoology and confirmed.

Check yourself

WebXam problem for today's skill

One exam-style question that uses exactly what you practiced today. Try it before you reveal the answer, then read why each choice is right or wrong.

WebXam-style domain: Molecular biology and diagnosticsSelf-check skill: Classifying a variant as pathogenic, benign, or VUS from database evidence

A lab finds an IRF6 change in one patient with a cleft. The change has never been reported in ClinVar, has no population frequency data, and no family members have been tested. How should it be classified right now, and what evidence would most help?

Tap an answer to see the full explanation. Nothing is recorded or graded.

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