Fig. 6.

Histograms of GERP++ (conservation) and Polyphen2(prediction) scores of RYR1 variants in the UW ESP and EMHG data sets.

Each of these panels graphs the indicated conservation score for variants in RYR1 from either a subset of the 5,379 UW ESP exomes or those labeled pathogenic by the EMHG.A) GERP++ scores for thenonintronic UW ESP exome variants with MAF < 1%. Vertical dashed line indicates the mean score (1.12) of these 535 variants; B) GERP++ scores for the 30 EMHG pathogenic variants. Vertical dashed line indicates the mean score,3.99; C) PolyPhen2 scores for missense UW ESP variants with MAF < 1%.The vertical dashed line is the mean score (0.726) of these 317 variants; D) PolyPhen2 scores for the 30 EMHG pathogenic variants.The vertical dashed line is the mean score, 0.997.European Malignant Hyperthermia Group = EMHG; Exome Sequencing Project = ESP; genomic evolutionary rate profiling = GERP; minor allele frequency = MAF; ryanodine receptor 1 gene = RYR1; University of Washington = UW.