SMAD7 was first reported in relation to autosomal dominant congenital heart disease in 2013 (Wang et al. 2013, PMID: 24039762). A missense variant reported in an individual with CHD was included in this curation (PMID: 24039762). There are more variants reported in individuals with CHD in two publications, all of which were synonymous variants that were not scored due to either low SpliceAI scores or high minor allele frequency (>0.00001) on gnomAD v.4 (PMID: 24039762, 28078173). This gene-disease relationship is also supported by expression data in mouse embryos and 2 mouse models showing heart defects (PMID: 18952608). In summary, there is limited evidence supporting the relationship between SMAD7 and autosomal dominant congenital heart disease. 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 May 13th, 2024 (SOP Version 10).
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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