Table 2.

Variants pathogenicity categorization.

References	Categorization	Interpretation
Dorschner et al., 2013	Pathogenic	Allele frequency of the identified variant is below cutoff AND segregation can be found in at least two unrelated families
	Likely pathogenic variant of uncertain significance (VUS)	Allele frequency of the identified variant is below cutoff AND identified in at least three unrelated individuals
	VUS	Allele frequency of the discovered variant is below cutoff AND present in less than three unrelated affected individuals
	Likely benign VUS	Allele frequency of the identified variant is below cutoff AND/OR seen in combination with a known pathogenic mutation
Richards et al., 2015 ACGM and AMP	Pathogenic very strong	Null variant (non-sense, frameshift, initiation codon, single or multiexon deletion) in a gene is a known mechanism of disease
	Pathogenic strong	Similar amino acid modification which was previously considered as pathogenic variant independent of nucleotide change
	Pathogenic moderate	Localize in a mutational critical region and very important functional domain without benign variation
	Pathogenic supporting	Cosegregation with disease located in many affected family members in a gene well known to be the cause the disease
	Benign standalone	Allele frequency is greater than 5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
	Benign strong	Allele frequency is greater than expected for disorder
	Benign supporting	Missense variant in a gene for which primarily truncating variants are known to cause disease