Fig. 1

Workflow chart of the NGS data re-analysis and criteria for variants inclusion. Schematic representation of the analytical pipeline adopted for NGS data re-analysis of the 114 patients included in the study, with a negative genetic diagnosis at the time of the first analysis. Filtering criteria and databases used to classify variants are indicated. Identified variants were included in a NGS genetic report. Whenever possible, variant(s) validation and family segregation studies were performed for a better variant(s) annotation and reported in a genetic report. Genetic reports were considered as conclusive, uncertain, or inconclusive based on the indicated criteria. C3: variant of unknown significance; C4: likely pathogenic variant; C5: pathogenic variant; AR: autosomal recessive