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Katherine Lafferty

Katherine Lafferty

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Disease

Developmental cardiac valvular defect

Inheritance

Autosomal recessive

Prevalence

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titlePossible sources

Orphanet

Medline Plus Genetics

 

Source:

Rapid or full curation?

  •  Rapid
  •  Full

ClinGen / GenCC / BabySeq / HGMD / OMIM

GenCC- cardiac valvular defect, developmental (Invitae: Strong, Ambry: Moderate)

OMIM- Cardiac valvular dysplasia 1

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

PMID: 33645542-

Multiple variants in multiple families:

pLOF variants - 6 x 2 points = 12 points

Missense variants w/o consanguinity, not in gnomAD - 15 x 0.5 = 7.5 points

Segregation Evidence:

PMID: 33645542-

Segregations: 8 total from multiple families (2 points)

Case/Control Evidence:

Experimental Evidence:

PMID: 27799408 (knockout mouse models show cardiac features)- Max points already hit

Source:

Clinical Validity Points Total

Source:

Clinical Validity Classification

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titleClassifications (pts)

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

Definitive

Source:

Molecular Mechanism

Expand
titleMechanisms

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function

PMID: 27799408

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

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

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

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