Note: AD=autosomal dominant; Hetero=heterozygosity; PVS1=null variant (nonsense, frameshift, canonical +- 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease PM1=Located in a mutational hot spot and/or critical and well established functional domain (e.g., active site of an enzyme) without benign variation; PM2=Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium; PM4=Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants; PP1=Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease; PP2=Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease; PP3=Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.) PP5=Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation; PP6=The user has additional 2 supporting pathogenic evidences.