TCAP was originally evaluated for DCM by the ClinGen DCM GCEP on 08/12/2020. Evidence of the association of this gene with DCM was re-evaluated using SOP v10 on 4/18/2025. As a result, the classification did not change. A summary of the information contributing to the classification of this gene at the time of re-evaluation is summarized herein.
At least 12 variants, including 11 heterozygous missense and 1 homozygous intron, have been reported in humans with DCM. These variants were identified in case-level and case-control data sets (Hayashi et al., 2004, PMID: 15582318; Hershberger et al., 2008, PMID: 19412328; Hirtle-Lewis et al., 2013, PMID: 24037902; Akinrinade et al, 2015, PMID: 26084686; Walsh et al, 2017, PMID: 27532257; Nguyen et al., 2021, PMID: 34011823; Alaei et al., 2023, PMID: 37752589). However, due to high minimal allele frequency and limited number of screened genes, three missense variants were scored. One case control study was scored.
In addition, this gene-disease association is supported by expression data and shared biochemical function and protein interaction with other genes known to be associated with DCM (i.e., TTN) (Valle et al, 1997, PMID: 9350988; Gregorio et al, 1998, PMID: 9817758). Though mouse models failed to recapitulate exact human DCM phenotypes, a zebra fish model partially recapitulate human DCM phenotypes (Knöll et al., 2011, PMID: 21799151; Ibrahim et al, 2013, PMID: 23100327; Zhao et al., 2024, PMID: 39226992).
In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of TCAP with AD DCM. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on April 18th, 2025 (SOP Version 10)
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