ADAM17 (formerly known as TACE) was FIRST reported in relation to autosomal dominant congenital heart disease in 2016 (Priest et al., PMID: 27058611). For this curation, variants in ADAM17 have been reported in individuals with the following phenotypes: Tetralogy of Fallot and atrioventricular septal defect. Of note, this gene has also been implicated in neonatal inflammatory skin and bowel disease (OMIM:614328). This will be assessed separately. At least six unique missense variants have been reported in humans with congenital heart disease; however, three of them were too frequent to cause disease. Evidence supporting this gene-disease relationship includes case-level data. Variants in this gene have been reported in at least five probands in two publications (PMIDs: 27058611, 30610007). This gene-disease relationship is supported by animal models and expression studies (PMIDs: 9812885, 12773386, 14499647, 15936750, 33957124). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date 08/14/2023 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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