The relationship between DSG2 and arrhythmogenic right ventricular cardiomyopathy (autosomal dominant) was evaluated using the ClinGen Clinical Validity Framework as of July, 2018. Variants in DSG2 were first reported in humans with this disease as early as 2006 (Pilchou et al., PMID: 16505173). Variation in DSG2 is a well-known cause of ARVC and accounts for 5%-26% of cases (McNAlly et al., 2005; PMID: 20301310). Since this gene-disease relationship is well-known, there is a significant amount of case-level data, segregation data and experimental data available in the literature, therefore the maximum score for both genetic evidence and experimental evidence has been reached. Note, this curation effort may not be exhaustive of all literature related to this gene-disease relationship. This gene-disease relationship is supported by animal models, in vitro assays, expression assays, and protein interactions. In summary, DSG2 is definitively associated with autosomal dominant ARVC. 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 September 14, 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).
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