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Disease

FORMAT: HEADING 1

Inheritance

Autosomal recessive / autosomal dominant / X-linked

Prevalence

Expand
titlePossible sources

Orphanet

Medline Plus Genetics

 

Source:

Rapid or full curation?

  •  Rapid
  •  Full

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

Expand
titleClassifications (pts)

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

Source:

Molecular Mechanism

Expand
titleMechanisms

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function / Gain of function / Dominant Negative

Penetrance

Expand
titleoptions

Complete (100%)

High (≥80%)

Moderate  (<80% and >20%)

Low (≤20%)

(list source/PMID)

Source:

Age of Onset

Expand
titleoptions

Congenital

Pediatric

Adolescent

Adulthood

Late adulthood

(list source/PMID)

Severity

Expand
titleOptions

Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete.
Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high.
Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced.
Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low.
None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers.

Clinical Features

Sources:

HPO Terms

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

Gene SOPs & Notes

CURATION FOR THE TG[11]T5 https://docs.google.com/document/d/1drRJf4CcMNOsrvyVutaPx9LNCVXXEim1A9FjXoebAnw/edit Located in intron 8.

Note that TG[11]T[5] in cis with Arg117His is a 3 star pathogenic variant in ClinVar (variant ID 209047) https://www.ncbi.nlm.nih.gov/clinvar/variation/209047/

You will likely need to review variants in IGV to determine the number of TGs and the number of Ts.

Nomenclature:

  • TG[11]T[5] will be called as c.1210-7_1210-6del (see case 47230812301141)

  • Likely the 12TG or 13TG variants will be called in the vcf as c.1210-34_1210-33dup (for 12TG) and c.1210-34_1210-31dup (13TG).

    • If they are TG[12]T[5} or TG[13]T[5], c.1210-7_1210-6del should also be present.

Curation Summary

Expand
titleExamples

- The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Variable expression or severity:
The severity and expressivity of the disorder is highly variable, even within families.
- If multiple conditions associated with the gene:
It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited

Case ID, Curator name, Date, Jira ticket link

Andrea Oza 04/05/24

  • 47230812301141

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