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Updated: Jun 20, 2026
07:15
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Reproducibility of the Evaluation of Genetic Variant Pathogenicity Based on the Animal Variant Classification
Iris Casselman1, Carlotta Ferrari2, Marie Abitbol3,4
1Laboratory of Animal Genetics, Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Merelbeke-Melle, Belgium.
Animal Genetics
|June 18, 2026
Summary
The Animal Variant Classification Guidelines (AVCG) improve genetic variant evaluation in veterinary medicine. Reproducibility of pathogenicity classification using AVCG is 65%, comparable to human guidelines, supporting its utility in animal genetics.
Area of Science:
- Veterinary Genetics
- Molecular Diagnostics
- Animal Disease Research
Background:
- Genetic variant pathogenicity assessment in animals historically lacked standardized guidelines, leading to inconsistent interpretations.
- The Animal Variant Classification Guidelines (AVCG) were introduced to provide a more objective framework for evaluating genetic variants in veterinary species.
- The International Society of Animal Genetics (ISAG)-endorsed Variant Pathogenicity Working Group (VPWG) utilizes the AVCG, assessing variants based on 23 criteria.
Purpose of the Study:
- To assess the reproducibility of the Animal Variant Classification Guidelines (AVCG) in classifying genetic variants for single-gene diseases in veterinary species.
- To evaluate the consistency of pathogenicity label assignment and clinical relevance determination by independent reviewers using the AVCG.
- To compare the reproducibility of AVCG classifications with those reported for human variant classification guidelines.
Main Methods:
- 150 published likely causal variants for single-gene diseases across dog, cat, and horse were independently and blindly assessed by three VPWG reviewers.
- Each reviewer applied the standardized AVCG criteria to evaluate the variants.
- Agreement on inclusion criteria and reproducibility of pathogenicity labels and clinical relevance were calculated.
Main Results:
- An overall agreement of 93% was achieved for decisions on whether variants met the inclusion criteria for AVCG evaluation.
- The reproducibility of pathogenicity label assignment was 65%, while the reproducibility of clinical relevance assessment was 83%.
- The reproducibility rates for AVCG are comparable to those reported for human variant classification guidelines.
Conclusions:
- The reproducibility of AVCG classifications by the ISAG-endorsed VPWG supports its utility and reliability in veterinary genetics.
- The AVCG provides a standardized and objective approach to genetic variant evaluation in animals, enhancing diagnostic consistency.
- Further validation and refinement of the AVCG can improve its application in diagnosing single-gene diseases in diverse veterinary species.
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