Tiered Classification Methology - Curated genotype and phenotype data is presented with a tiered classification of genes based on the number of de novo pathogenic loss-of-function (pLOF) variants. These variants are defined as LOF nonsense, splice site, and frameshift sequence variants and single gene deletions that include one or more exons. Candidate genes have been ranked into four tiers based on the strength of evidence, as outlined below.
Genes with three or more de novo pathogenic loss-of-function variants
Genes with two de novo pathogenic loss-of-function variants
Genes from tiers 1 and 2 are considered high confidence DBD causative genes
Genes with one de novo pathogenic loss-of-function variant
Genes with only inherited (or unknown inheritance) pathogenic loss-of-function variants
Genes from tiers 3 and 4 are categorized as emerging DBD causative genes