Twenty-one papers were reviewed related to JUP and ARVC (2945574, 21668431, 2945574, 9610536, 18937352, 10902626, 15851108, 27170944, 11691526, 16893920, 29802319, 31275992, 25820315, 25820315, 25765472, 25705887, 25087486, 21668431, 20130592, 17924338, 20031617). The initial discovery of a homozygous two-nucleotide deletion (c.2038_2039delTG; p.Trp680Gly_fs) in JUP underlying Naxos disease, which includes ARVC with palmoplantar keratoderma and woolly hair, led to further focus on this and other desmosome genes in non-syndromic ARVC (McCoy et al, PMID 10902626). Murine models support the functional, arrhythmic, and histopathologic cardiac effects from loss-of-function variants in Jup (PMID 27170944; 25705887). Heterozygous pathogenic variants in JUP account for a low percentage of non-syndromic ARVC (0.5%; PMID 25820315). Despite the relatively low percentage, null and missense variants have evidence of impact in multiple families with ARVC. This leads to strong genetic evidence for the role of pathogenic variants in JUP for dominant, non-syndromic ARVC (score 10.5). The experimental evidence supports this association (score 5.5), with final classification: Strong.
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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