Inheritance

Autosomal dominant

Prevalence

Source:

Rapid or full curation?

ClinGen / GenCC / BabySeq / HGMD / OMIM

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

Segregation Evidence:

Case/Control Evidence:

Experimental Evidence:

Source:

Clinical Validity Points Total

Source:

Clinical Validity Classification

Source:

Molecular Mechanism

Loss of function / Gain of function / Dominant Negative

Tandem repeat expansion - CAG/CAA (polyglutamine) in the coding region of exon 3. CAA interruptions are normally present in primarily CAG repeat.

• In the interest of time for the ExpansionHunter validation, I am setting the normal max at 40 based on the resources below. I only need this value for specificity, so we can adjust for reporting purposes in the future.

Review:

• Stripy: Normal - 25-42, pathogenic ≥43

• Gnomad: Normal ≤ 42, Pathogenic ≥ 43

• STRchive: Normal max 40, pathogenic min 49

• GeneReviews - normal 25-40, reduced penetrance 41-48, full penetrance >48

•  

Penetrance

(list source/PMID)

Source:

Age of Onset

(list source/PMID)

Severity

Clinical Features

Sources:

HPO Terms

https://hpo.jax.org/app/

Gene SOPs & Notes

 LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant

Curation Summary

Case ID, Curator name, Date, Jira ticket link