dbSNP ID, reference Single Nucleotide Polymorphism Identification number. Individual variations are identified by an 'rs' prefix followed by a unique numeric string. ACMG/AMP, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. PVS1, null variant in a gene where loss of function is a known mechanism of disease. PS4, the prevalence of the variant in affected individuals is significantly increased compared to the prevalence in controls. PM1, variant located in a mutational hot spot and/or critical and well-established functional domain without benign variation. PM2, absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes or ExAC. PM5, novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before. PP2, missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PP3, multiple lines of computational evidence support a deleterious effect on the gene or gene product.

Source: Prepared by the authors of this study.