Table 3.

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

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 Benign	- Epidemiological and bioinformatics data indicate that the variant is not pathogenic. - These variants are commonly not reported but might be available on request.