The Novel Association of a Single Nucleotide Variant in the COL3A1 Gene with Diffuse Coronary Aneurysms.

The COL3A1 gene, encoding the pro-alpha chain of type III collagen, has been implicated in a range of collagen-mediated diseases such as Ehlers-Danlos syndrome and aortic aneurysms. In this report, we present evidence for the first time associating a single nucleotide variant p.P517R in exon 22 of COL3A1 with the development of diffuse coronary aneurysms in a human subject without prior atherosclerotic cardiovascular disease, connective tissue disorder, or phenotypic characteristics diagnostic for vascular Ehlers-Danlos syndrome. Computational modeling of this specific variant in AlphaFold and in silico analyses predict deleterious alterations in the structure and function of the COL3A1 gene product, alpha 1 chain of type III collagen. This novel phenotype-to-genotype correlation should prompt further investigation into the mechanistic basis of this association.