| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Congenital Heart Defect v0.446 | ERBB2 | Bryony Thompson Marked gene: ERBB2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.446 | ERBB2 | Bryony Thompson Gene: erbb2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.446 | ERBB2 | Bryony Thompson Classified gene: ERBB2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.446 | ERBB2 | Bryony Thompson Gene: erbb2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital Heart Defect v0.445 | ERBB2 |
Eleanor Ludington gene: ERBB2 was added gene: ERBB2 was added to Congenital Heart Defect. Sources: Literature Mode of inheritance for gene: ERBB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ERBB2 were set to 40329538 Phenotypes for gene: ERBB2 were set to Congenital heart disease - left ventricular outflow tract obstruction defects; MONDO:0005453 Review for gene: ERBB2 was set to AMBER Added comment: A missense single-nucleotide variant in ERBB2 (chr17:39717377 C>T, NM_004448.4:c.1795C>T, p. Arg599Cys (GRCh38), rs369903296) was identified in 3 unrelated Finnish probands with left ventricular outflow tract obstruction defects. - all 3 probands were familial cases with multiple affected family members - all 3 probands had severe phenotypes (diagnosed either prenatally or in the first days of life) - Proband of family 1: hypoplastic left heart syndrome (HLHS; including BAV, hypoplastic aortic arch, coarctation of the aorta, ASD, left superior vena cava) - Proband of family 2: Shone's complex and VSD including aortic valve stenosis, mitral stenosis, coarctation of the aorta - Proband of family 3: HLHS (including mitral valve stenosis, BAV, aortic valve stenosis, muscular VSD) The variant segregated in affected family members of each proband who had other less severe congenital heart disease - Family 1 grandfather - coarctation of the aorta - Family 2 mother - coarctation of the aorta, BAV - Family 3 mother - coarctation of the aorta, BAV - Family 1 father - BAV - Family 2 maternal grandfather - asymmetric aortic valve The variant also segregated in two unaffected family members in family 2, suggesting reduced penetrance. The variant is present in gnomAD with a total allele frequency of 0.00009372 in Finnish Europeans and 0.000004340 across all populations. Supportive functional assays and a Zebrafish model was conducted. Sources: Literature |
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