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Table 3 Classification of genetic variants in routine diagnostics, leaned on the criteria suggested by the American College of Medical Genetics [28]

From: Genetic testing in inherited endocrine disorders: joint position paper of the European reference network on rare endocrine conditions (Endo-ERN)

Clinical significance Pathogenicity classes Major Criteria
Clinical significance Pathogenic
Likely pathogenic
- The variant affects the structure and function of the gene/protein.
- The variant affects a gene in which similar variants are known to be disease-causing.
- The pathogenic nature of the variant is supported by epidemiological data, bioinformatic prediction and segregation analyses.
Uncertain significance Variant of unknown significance (VUS) - Not all parameters of pathogenicity are fulfilled.
- Bioinformatics prediction of pathogenicity but without final confirmation.
No clinical significance Likely benign
- Epidemiological and bioinformatics data indicate that the variant is not pathogenic.
- These variants are commonly not reported but might be available on request.