There is moderate evidence that CDH2 is associated with ARVC. The first publication that associated TJP1 with ARVC was published in 2017 (28280076) and described two families: one family with five affected with p.Gln229Pro. The phenotype was consistent with ARVC. The second family was one proband with clear ARVC phenotype that carried p.Asp407Asn. A second publication in 2017 also identified in a Norwegian family the same variant, p.Asp407Asn in a family with biventricular ARVC phenotype. There is some experimental evidence in a KO mouse (15662031) that that CDH2 disruption leads to dissolution of desmosomes and area composite, cardiomyopathy, VT, and SCD. However, these are not missense variants as reported in the patients. There is emerging evidence that CDH2 mutations are associated with an ARVC phenotype, but additional information on mechanisms of disease, and pathogenicity of missense vs. truncating variants is still missing.
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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