HAND2 was first reported in relation to autosomal dominant structural congenital heart disease HAND2-related in 2015 (Lu et al., 2015; PMID: 26676105). Two variants (missense variants that cause loss of function) that have been reported in two probands in two publications (PMIDs: 26676105, 26865696) are included in this curation. Variants associated with isolated dilated cardiomyopathy are excluded. The mechanism of pathogenicity is reported to be loss of function. This gene-disease relationship is also supported by experimental evidence (mouse models, expression studies, biochemical functional evidence, and interaction evidence; PMIDs: 9171826, 9878849, 10675351, 11812799, 15576406, 26676105). In summary, there is moderate evidence supporting the relationship between HAND2 and autosomal dominant structural congenital heart disease. 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 7/17/2023 (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).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.