Exome-wide MTR scores computed with RGC-ME data for all possible missense variants in canonical transcripts

Exome-wide missense tolerance ratio (MTR) scores computed with RGC-ME exome sequencing data for all possible missense variants in canonical transcripts. Coordinates are in hg38. Variants are labeled “uid” and follow the format CHR:POS:REF:ALT. Other fields include: Ensembl v100 transcript ID, gene name, gene ID, exon number, amino acid position (“aa_position”), adjusted tri-nucleotide context mutation rate (“adj_rate”), and protein length. Parameters for computing MTR at each variant include the expected (“synExp” and “misExp”, resulting in the MTR denominator “expMTR”) and observed (“synObs” and “misObs”, resulting in the MTR numerator “obsMTR”) counts of missense and synonymous variants in each 31-codon window centered on possible missense variants exome-wide using data from 822K related individuals. Computed MTR values for all missense variants, p-value from binomial test, and FDR corrected q-value are included. MTRPercentile_exome and MTRPercentile_transcript represent the percentile rank of MTR score across the exome and per transcript, respectively. Regions with long, continuous regions of median MTR=0 as defined by segmentation were removed as likely artifacts stemming from lack of high-quality observed variants. A small number of genes retained MTR=0 segments because there were sufficiently high counts of observed synonymous variants relative to the lack of missense variants.<br>