PRKD1 was first reported in relation to autosomal dominant congenital heart disease in 2021 (Reuter et al. 2016, PMID: 34328347). Two variants (frameshift) that have been reported in 2 probands in 2 publications (PMIDs: 34328347, 36478645) are included in this curation. The split curation for autosomal recessive congenital heart disease has been curated separately. There are more variants reported in individuals with CHD in 16 publications, all of which were not scored due to a high minor allele frequency (>0.00001) in gnomAD v.4, inheritance from unaffected parents, the variant being a copy number variant containing additional genomic material, the proband having additional variants in genes associated with congenital heart disease, and/or the proband having a syndromic phenotype (PMID: 25713110, 27479907, 28991257, 31453292, 31130284, 30149741, 33131162, 32817298, 33919081, 32368696, 34328347, 36308391, 34983622, 35885997, 37035742, 36568277). The mechanism of pathogenicity appears to be unclear. This gene-disease relationship is also supported by expression data in mouse embryos and protein interaction data (PMID: 31784580). In summary, there is limited evidence supporting the relationship between PRKD1 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 April 30th, 2024 (SOP Version 10)
PRKD1 was first reported in relation to autosomal dominant congenital heart disease in 2021 (Reuter et al. 2016, PMID: 34328347). Two variants (frameshift) that have been reported in 2 probands in 2 publications (PMIDs: 34328347, 36478645) are included in this curation. The split curation for autosomal recessive congenital heart disease has been curated separately. There are more variants reported in individuals with CHD in 16 publications, all of which were not scored due to a, a high minor allele frequency (>0.00001) in gnomAD v.4, inheritance from unaffected parents, the variant being a copy number variant containing additional genomic material, the proband having additional variants in genes associated with congenital heart disease, and/or the proband having a syndromic phenotype (PMID: 25713110, 27479907, 28991257, 31453292, 31130284, 30149741, 33131162, 32817298, 33919081, 32368696, 34328347, 36308391, 34983622, 35885997, 37035742, 36568277). The mechanism of pathogenicity appears to be unclear. This gene-disease relationship is also supported by expression data in mouse embryos and protein interaction data (PMID: 31784580). In summary, there is limited evidence supporting the relationship between* PRKD1 *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 April 30th, 2024 (SOP Version 10)
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