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Research article2024Peer reviewedOpen access

Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines

Boeykens, Frederique; Abitbol, Marie; Anderson, Heidi; Dargar, Tanushri; Ferrari, Paolo; Fox, Philip R.; Hayward, Jessica J.; Haggstrom, Jens; Davison, Stephen; Kittleson, Mark D.; van Steenbeek, Frank; Ljungvall, Ingrid; Lyons, Leslie A.; Longeri, Maria; Ohlsson, Asa; Peelman, Luc; de Citres, Caroline Dufaure; Smets, Pascale; Turba, Maria Elena; Broeckx, Bart J. G.


Introduction The correct labeling of a genetic variant as pathogenic is important as breeding decisions based on incorrect DNA tests can lead to the unwarranted exclusion of animals, potentially compromising the long-term health of a population. In human medicine, the American college of Medical Genetics (ACMG) guidelines provide a framework for variant classification. This study aims to apply these guidelines to six genetic variants associated with hypertrophic cardiomyopathy (HCM) in certain cat breeds and to propose a modified criterion for variant classification. Methods Genetic samples were sourced from five cat breeds: Maine Coon, Sphynx, Ragdoll, Devon Rex, and British Short- and Longhair. Allele frequencies were determined, and in the subset with phenotypes available, odds ratios to determine the association with HCM were calculated. In silico evaluation followed with joint evidence and data from other publications assisting in the classification of each variant. Results Two variants, MYBPC3:c.91G > C [A31P] and MYBPC3:c.2453C > T [R818W], were designated as pathogenic. One variant, MYH7:c.5647G > A [E1883K], was found likely pathogenic, while the remaining three were labeled as variants of unknown significance. Discussion Routine genetic testing is advised solely for the MYBPC3:c.91G > C [A31P] in the Maine Coon and MYBPC3:c.2453C > T [R818W] in the Ragdoll breed. The human ACMG guidelines serve as a suitable foundational tool to ascertain which variants to include; however, refining them for application in veterinary medicine might be beneficial.


cardiac disease; feline genetics; variant classification; ACMG guidelines; genetic diversity

Published in

Frontiers in Veterinary Science
2024, Volume: 11, article number: 1327081