Traynelis J.,* Silk M.,* Wang Q., Berkovic S.F., Liu L., Ascher D.B., Balding D.J., Petrovski S. (2017). Optimizing genomic medicine in epilepsy through a gene-customized approach to missense variant interpretation. Genome Research (2017)
The MTR aims to quantify the amount of purifying selection acting specifically on missense variants in a given window of protein-coding sequence. It is estimated across sliding windows of 31 codons (default) and uses observed standing variation data from the WES component of the Exome Aggregation Consortium Database (ExAC), version 2.0 (http://gnomad.broadinstitute.org)
HGNC symbols resolve to a canonical-defined transcript, as defined by Ve!P. If one is not defined, then the longest protein-coding sequence transcript with a valid CCDS in Ensembl v75 is selected. Alternatively, users can directly enter a Ensembl ENST (v75) transcript.
Each window’s MTR estimate is supplemented with a study-wide false discovery rate adjusted binomial exact test for deviation from MTR=1 (where the standing variation observed proportion equals the expected proportion of missense variants). Red MTR regions denote windows achieving a FDR < 0.10.
Gaps in MTR plots align with windows where the total observed standing variation < 3; commonly reflecting inadequate sequencing coverage in the standing variation sample.
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