CTF1

Inheritance Pattern: AD

Disease ID:MONDO:0005021

Submitter: ClinGen

CTF-1 was originally evaluated for DCM by the ClinGen DCM GCEP on February 28, 2020. Evidence of the association of this gene with DCM was re-evaluated using SOP v10 on June 14 2024. The overall genetic evidence points decreased at recuration. With these updates, the clinical validity classification did not change and remains Limited. A summary of the information contributing to the classification of this gene at the time of re-evaluation is summarized herein. CTF-1 was first reported in relation to autosomal dominant dilated cardiomyopathy in 2000 (Erdmann J et al, PMID: 11058912). Human genetic evidence supporting this gene-disease relationship includes case-level data. At least 7 variants (6 missense and 1 spice site variant) have been reported in humans. Variants in this gene have been reported in at least 10 probands in 3 publications (Erdmann et al, 2000, PMID: 11058912; Pugh et al, 2014, PMID: 24503780; Akinrinade et al, 2015, PMID: 26084686). No segregation data has been reported. This gene-disease relationship has been studied in at least one case-control study at the single variant level (Erdmann et al, 2000, PMID: 11058912), however, this variant was subsequently found to be more commonly expressed in the population than would be expected to explain disease. There is a lack of robust human genetic evidence demonstrating this gene-disease relationship in the literature. No new publications demonstrating CTF-1 variants in DCM were identified during re-curation. Evaluation of the previously identified variants found that all but one of the variants have subsequently been found at a frequency higher than would be expected for a monogenic, pathogenic effect in population reference data sets. This gene-disease association is supported by one animal model (rat) and expression studies (Pennica et al, 1995, PMID: 7862649; Pennica et al, 1996, PMID: 8833032; Zolk et al, 2002, PMID: 12234945; Lopez et al, 2014, PMID: 24366078; Robador et al, 2011, PMID: 21771897; Lopez-Andres et al, 2012, PMID: 22733458). Two additional human expression studies (Sharif et al, 2021, PMID: 34447655; Rubiś et al, 2021, PMID: 34071085) were identified during re-curation. In summary, no convincing evidence for a causal role for CTF-1 and autosomal dominant DCM has been reported. Although this gene-disease assertion is supported by one animal model (rat) and multiple expression studies (human) no reports have directly implicated the gene in humans. Additionally, there has been a lack of new supporting evidence in the four year period since the previous curation. In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of CTF-1 and AD DCM.This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group on June 14 2024 (SOP Version 10).

Inheritance Pattern: AD

Disease ID:MONDO:0016333

Submitter: G2P