PRKD1 was first reported in relation to autosomal recessive congenital heart disease in 2015 (Shaheen et al. 2016, PMID: 25713110). Three variants (nonsense, splicing) that have been reported in 3 probands in 3 publications (PMIDs: 25713110, 31130284, 33919081) are included in this curation, but only two variants (nonsense) were scored, as the other variant was present in unaffected family members.The split curation for autosomal dominant congenital heart disease has been curated separatelyThere are more variants reported in individuals with CHD in 14 publications, all of which were not scored due to a (PMID: 33131162, 32817298, 27479907, 28991257, 30149741, 31453292, 32368696, 34328347, 36308391, 34983622, 35885997, 36478645, 37035742, 36568277). The mechanism of pathogenicity is reported to be loss-of-function. This gene-disease relationship is also supported by expression data in mouse embryos (PMID: 31784580), protein interaction data (PMID: 31784580), and a mouse model showing heart defects (PMID: 38419169). In summary, there is limited evidence supporting the relationship between PRKD1 and autosomal recessive 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 April 30th, 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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