The relationship between TMEM43 and arrhythmogenic right ventricular dysplasia (autosomal dominant) was evaluated using the ClinGen Clinical Validity Framework as of July 10th, 2019. Variants in TMEM43 were first reported in humans with this disease as early as 2008 (Merner et al., PMID 18313022). At least 9 variants (mostly missense) have been reported in humans. However, the pathogenicity of most of the variants is unknown. The majority of genetic evidence comes from case-level data and segregation data for one founder variant, p.Ser358Leu, which has been reported in more than 20 families with ARVC and occurred de novo in one individual (Merner et al., 2008, PMID 18313022; Christensen et al. 2011, PMID 21214875; Baskin et al., 2013, PMID 23812740; Hodgkinson et al., 2013, PMID 22725725; Milting et al., 2014, PMID 24598986). This gene-disease relationship is also supported by an animal model, expression stuies, and in vitro assays. In summary, TMEM43 is definitively associated with autosomal dominant arrhythmogenic right ventricular dysplasia . This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Arrythmogenic Right Ventricular Cardiomyopathy Gene Curation Expert Panel on October 26, 2018 (SOP Version 6).
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.