NTRK3 was first reported in relation to autosomal dominant congenital heart disease in 2014 (Werner et al. 2014, PMID:25196463). At least five unique missense variants in five individuals with congenital heart disease were reported in a publication (PMID: 25196463). Evidence disputing this gene-disease relationship includes case-level data. None of the five variants reported were scorable, as four were too frequent on gnomAD (MAF> 0.00001) to cause disease and one had an unaffected carrier mother. This gene-disease relationship is supported by expression data and two mouse models (PMIDs: 19187638, 9405689, 14550777). In summary, the evidence supporting the relationship between NTRK3 and autosomal dominant congenital heart disease has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role NTRK3 plays in this disease. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date February 6th, 2024 (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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