Interpreting MYH11 Copy Number Variation in Thoracic Aortic Aneurysm and Dissection

Thoracic aortic aneurysm and dissection (TAAD) is a rare but often fatal vascular disease. A family history of TAAD increases risk, and several genes are linked to risk of both aneurysm and dissection. The current AHA/ACC guidelines for management of TAAD include genetic testing for affected individuals with no other risk factors such as hypertension or bicuspid aortic valve. However, interpretation of genetic testing results, even for validated TAAD genes, can be challenging. Herein we show 2 TAAD cases in patients with MYH11 copy number variations. These cases demonstrate that MYH11 deletion is often miscategorized as pathogenic, while MYH11 duplication is miscategorized as benign. We then confirm the association of chromosome 16p13.1 duplications which include MYH11 and aortic dissection in the UK Biobank clinical registry. These cases underscore the risk of misannotation of MYH11 structural variants in the evaluation of genetic risk for TAAD patients.