ISHMap

ISHMap (In Silico Hotspot Map) reports deep intronic regions where single nucleotide substitutions are predicted to disrupt splicing more often than expected by chance. Every possible substitution in the introns of about 5,000 disease-associated genes is scored by in silico mutagenesis, and intervals enriched for spliceogenic variants are called as hotspots after Benjamini-Hochberg correction.

Hotspots matter for therapy as much as for diagnosis. Variants that cluster in one interval can share a single antisense oligonucleotide, so one molecule can correct several variants carried by unrelated patients. The approach and its experimental validation in COL4A5 are described in the accompanying preprint.

The browser gives, per gene, the summary statistics, the hotspot table with GRCh38 coordinates and q-values, and an intron view of the scored variants against the MANE Select transcript. Per-gene hotspot tables can be downloaded directly; the complete release, including the full variant tables and plots, is archived on Zenodo.

The interactive browser and the Zenodo record are in preparation. This page will link to them once they are published.