The TNNI3 gene was originally evaluated for DCM by the ClinGen DCM GCEP on 05/22/2020 for autosomal dominant DCM. Evidence of the association of this gene with DCM was re-evaluated using SOP v10 on 3/7/2025. As a result, the classification changed. A summary of the information contributing to the classification of this gene at the time of re-evaluation is summarized herein. Human genetic evidence supporting this gene-disease relationship includes case-level data. At least 17 variants have been reported in humans with DCM with the vast majority being missense variants. In addition, this gene-disease assertion is supported by expression studies, in vitro functional assays, protein interaction studies and studies showing rescue in patient cells (PMID: 2226790, 19590045, 29093449, 28436080, 36157491).
In summary, there is strong evidence to support the relationship between TNNI3 and AD DCM. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on 4/18/2025 (SOP Version 10).
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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