The TCAP gene was first associated with hypertrophic cardiomyopathy (HCM) in 2004 with missense variants found in 2 probands (Hayashi et al, PMID 15582318). Three subsequent studies have identified missense variants in 6 probands (Bos et al, 2006, PMID 16352453; Andersen et al, 2009, PMID 19035361; Toste et al. 2020, PMID 32565061). None of these variants have functional evidence in support of pathogenicity. Furthermore, 1 variant (2 probands) is common in the population (Bos et al, 2006, PMID 16352453), and 2 co-occurred with other variants (pathogenic TNNI3 variant, Andersen et al, 2009, PMID 19035361; VUS in MYBPC3, Bos et al. 2006, PMID 16352453). The mechanism for disease is unknown. The gene-disease association is supported by expression data (Valle et al. 1997, PMID 9350988; Fagerberg et al. 2014, PMID 24309898, Uhlen et al. 2015, PMID:25613900) and an interaction with CSRP3 (Knoll et al. 2002, PMID 12507422; Vafiadaki et al. 2014, PMID 24860983) which has moderate evidence for HCM. In summary, the evidence supporting the relationship between *TCAP *and HCM has been DISPUTED. More evidence is needed to either support or entirely refute the role *TCAP *plays in this disease. This gene-disease relationship was originally approved by the ClinGen Hypertrophic Cardiomyopathy Gene Curation Expert Panel on November 1, 2016. This gene-disease relationship was reevaluated on September 14, 2022 by the Hereditary Cardiovascular Disorders GCEP. As a result of this reevaluation, the classification changed from LIMITED to DISPUTED.
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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