SMC3 was first reported in relation to autosomal dominant Cornelia de Lange syndrome as early as 2007 (Deardorff et al., PMID: 17273969). At least 17 unique variants including missense, in-frame indel, and nonsense variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 17 probands, with 9 included in this curation to reach a definitive classification (PMID: 17273969, 25125236, 25655089, 25574841, 28781842). Variants in this gene segregated with disease in 1 additional family member. The mechanism of disease is proposed to be dominant negative. This gene-disease association is supported by an animal model, protein interactions, and in vitro functional assays (PMID: 18996922, 11983169, 23106691, 28408410). In summary, SMC3 is definitively associated with autosomal dominant Cornelia de Lange syndrome.
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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