SERPINC1 was first reported in relation to antithrombin III deficiency in 1984 (Koide T, et al., 1984, PMID: 6582486). Antithrombin III deficiency is predominantly inherited in an autosomal dominant manner however several biallelic cases have been reported, typically with a more severe presentation, as such the gene-disease relationship has been evaluated for semidominant inheritance. At least 400 unique variants (including missense, nonsense, splicing and frameshift 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 18 probands in 6 publications (PMIDs: 6582486, 7734360, 29747524, 28317092, 28892658, 21325262). Variants in this gene segregated with disease in 22 additional family members. More evidence is available in the literature, but the maximum score for genetic evidence has been reached. This gene-disease relationship is supported by its biochemical function in the regulation of blood coagulation (PMID: 4738234), the functional alteration observed in patient cells (PMID: 7734360), and both null and knock-in mouse models which recapitulate the more severe phenotypes observed in humans (PMID: 11018075 and PMID: 14592998). In summary, SERPINC1 is definitively associated with semidominant antithrombin III deficiency. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.
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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