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Gene-disease assertions not curated here (add link or write note): AR developmental and epileptic encephalopathy
Disease | Congenital Heart Disease |
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Inheritance | Autosomal dominant |
Prevalence | Generally quoted as 1/100 (common). Source: https://www.cdc.gov/ncbddd/heartdefects/data.html#:~:text=Number%20of%20U.S.%20Babies%20Born,year%20in%20the%20United%20States. |
Rapid or full curation? | |
ClinGen / GenCC / BabySeq / HGMD / OMIM | Not in ClinGen or BabySeq. GenCC: No submissions for AD CHDs. Three submissions for AR developmental and epileptic encephalopathy (strong by Invitae, moderate by Illumina, supportive by Orphanet). OMIM: AR Developmental and epileptic encephalopathy. HGMD: Curated variants below. |
Clinical Validity Scoring Notes and points | Many repeat cases using the Pediatric Cardiac Genetics Consortium (PCGC). CAD c.364C>T p.R122W Absent from GnomAD v4. REVEL: 0.947 PMID 26785492: Observed in 1-00129. De novo. Patient had a complex cardiac phenotype including: ASD, VSD, transposition of the great arteries, hypoplastic pulmonary arteries, parachute mitral valve, pulmonary stenosis, developmental delay, learning difficulty, macrocephaly, congenital Blindness, retinitis pigmentosa, chorioretinal atrophy, undescended testis, congenital scoliosis, small stature, static encephalopathy. (0.35 points) PMID: 28991257, PMID: 28191890, PMID: 31941532, PMID: 32368696: Looks like the same case as PMID 26785492.
CAD c.2782C>G p.L928V Absent from GnomAD v4. REVEL: 0.551 PMID 26785492: Observed in 1-04215. De novo. Patient had atrial septal defect, left aortic arch, developmental delay, esotropia, umbilical hernia, abnormal thumb, cafe au lait spots, hemangioma. (0.35 points) PMID: 28991257, PMID: 28191890, PMID: 31941532, PMID: 32368696: Looks like the same case as PMID 26785492.
CAD c.6432G>A p.M2144I Absent from GnomAD v4. REVEL: 0.645 PMID 26785492: Observed in 1-00200. De novo. Patient had transposition of the great vessels, tricuspid regurgitation, tricuspid valve abnormality, ventricular septal defect, ventricular inversion. (0.35 points) learning disabilities PMID: 28991257, PMID: 28191890, PMID: 31941532, PMID: 32368696: Looks like the same case as PMID 26785492.
CAD p.R842fs (2:27454972G>GT) CAD p.S1872fs (2:27463800CCT>C) PMID: 28991257: Patient 1-13318 with conotruncal defect, EM, unknown NDD. Heterozygous, transmitted. Not scored.
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Clinical Validity Points Total | 1.05 |
Clinical Validity Classification | Expand |
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| title | Classifications (pts) |
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| Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed |
| Limited. Source: |
Molecular Mechanism | Expand |
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| Loss of function Gain of function Dominant negative Unknown Other |
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Penetrance | Expand |
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| Complete (100%) High (≥80%) Moderate (<80% and >20%) Low (≤20%) |
(list source/PMID) | |
Source: Age of Onset | Expand |
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| Congenital Pediatric Adolescent Adulthood Late adulthood |
(list source/PMID) | |
Severity | Expand |
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| 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. |
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Clinical Features | Sources: |
HPO Terms https://hpo.jax.org/app/ | |
Gene SOPs & Notes | https://docs.google.com/document/d/1XY2_T3IJ7mtVPSrC6dCWmV2gqgqJ2p1laVBGZySK7vM/edit |
Curation Summary | Expand |
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| - 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 |
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Case ID, Curator name, Date, Jira ticket link | Case ID: SDSM-8F/SDOR-55/PDO-33275/E3710449173 Curator: Areesha Salman Date: 12/8/2023 |