Note: Described from the guidlines of ACMG. Very strong evidence of pathogenicity: PVS1: Loss of function (LOF) caused null variant (nonsense, frameshift, canonical +/−1 or 2 splice sites, initiation codon, single or multi-exon deletion) in a gene led to disease. Strong evidence of pathogenicity: PS1: A previously pathogenic resulted by same amino acid change regardless of nucleotide changing; PS3: Functional studies in vitro or in vivo supported a damaging effect on the gene or gene product; PS4: Comparing with the prevalence in controls, the prevalence of the variants in affected individuals is significantly increasing; Moderate evidence of pathogenicity: PM1: The functional domain located in a mutational hot spot hadn't benign variation; PM2: Absent from controls (or at extremely low frequency if recessive) in 1000 Genomes or ExAC; PM5: Novel missense changing in an amino acid residue differentiated from pathogenic missense reported before. Supporting evidence of pathogenicity: PP1: Disease resulted by known genes cosegregated with family members; PP2: Missense variants in a gene had a low rate of benign missense variation that are a common mechanism of disease; PP3: Several computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc); PP4: Patient's phenotype and their trios were highly specific for a disease with a single genetic etiology. p=pathogenic; LP=likely pathogenic; DM=damaging mutations.