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

## TL;DR

A new genetic variant in the COL3A1 gene is linked to diffuse coronary aneurysms in a person without known risk factors.

## Contribution

This is the first report linking the p.P517R variant in COL3A1 to diffuse coronary aneurysms.

## Key findings

- The p.P517R variant in COL3A1 is associated with diffuse coronary aneurysms in a subject without atherosclerosis or connective tissue disorders.
- Computational models suggest the variant alters the structure and function of type III collagen.
- The findings suggest a novel genotype-phenotype correlation for COL3A1-related disease.

## Abstract

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.