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

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.