FGF8 was first reported in relation to autosomal dominant congenital heart disease in 2020 (Zhou et al., PMID 32664970). Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we found no difference in molecular mechanism and inheritance pattern. Therefore, these disease entities have been lumped into one disease entity, autosomal dominant congenital heart disease. Evidence for association with hypogonadotrophic hypogonadism was not included in the curation. At least two rare missense variants have been reported in two probands in one publication (PMID: 32664970) and are included in this curation using an allele frequency threshold of 1x10-5. This gene disease relationship is supported by expression studies, protein interaction studies and animal models (PMIDs 7768185, 32664970, 10603341, 19509466, 9462741, 10603341, 12223415). There was additional experimental evidence that was not scored due to reaching the maximum experimental points. In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date 5/7/2024 (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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