Table 1

Software that were used in this study to evaluate conservation, minor allele frequency and potential damage of variants on splicing and protein structure and function

Conservation1. MutationAssessor
2. Exome Variant Server database
Allele frequency1. Exome Variant Server
2. 1000 Genomes
3. Variant Effect Predictor at the Ensembl genome browser
Known polymorphism and common variants were excluded. We used a minor allele frequency (MAF) cut-off of 0.2% for variants in genes with AD and XL disease inheritance, and 0.5% for variants in genes with AR inheritance
Predict potential damage of amino acid substitution on protein structure and function1. Polymorphism Phenotyping 2 (PolyPhen2)
2. Sorting Intolerant From Tolerant (SIFT)
3. Sorting Intolerant From Tolerant (SIFT)—Indel
4. Protein Variation Effect Analyzer (Provean)
5. MutationTaster
Predict potential damage on splicing1. Human Splicing Finder 3.0
2. MutationTaster
Reported disease-causing mutations1. SNP effect 4.0
2. The National Center for Biotechnology Information's ClinVar database
3. the Leiden Open Variation Database (LOVD)
4. Fanconi Anemia Mutation database
5. The Telomerase Database