Question about plotting splice site mutations

[bailee-kain]

Hello!

I am using the visualizing "Mutation mapper" tool on the cBioportal website, and I keep having an issue where the splice site mutations do not show up in the appropriate place in the gene body, but rather at the beginning of the gene. Is there a way to fix this? I am defining the mutations as splice site mutations and using c. prior to the splice site mutation, but that only seems to solve the problem for certain splice site mutations and not others. Any insight to solve this issue would be greatly appreciated!

[SophiaLi20]

some steps and insights to help you resolve the issue:

1. Verify Mutation Annotation Format
   The cBioPortal Mutation Mapper can identify splice site mutations when they are correctly annotated in your dataset.
   Employ standardized formats to describe splice site mutations (such as HGVS nomenclature). Examples include:
   g.
   to indicate genomic location.
   c.
   to denote coding DNA sequence location (e.g.,
   c.IVS2+1G>A
   for an intronic splice mutation).
   Ensure consistent definition of intronic splice mutations using accepted formats (like
   c.IVS
   or explicit
   c.
   coordinates).
2. Indicate Mutation Types
   Ensure that mutations are explicitly labeled as "Splice Site" in the data you're uploading. For custom mutation files, confirm that the
   Mutation_Type
   column designates "Splice_Site" for these mutations.
3. Confirm Reference Genome and Transcript
   Make sure mutations are aligned with the correct reference genome version (such as GRCh37 or GRCh38) and the appropriate transcript for the gene in question. Misalignment can lead to incorrect mutation mapping.
4. Examine Tool-Specific Behavior
   Mutation Mapper may misplace mutations if it cannot accurately interpret their position. If some splice site mutations display correctly while others don't, investigate:
   Any differences in formatting or nomenclature in the input file.
   Whether incorrectly displayed mutations are near boundaries (such as exon-intron junctions).
5. Perform Manual Validation of Mutation Locations
   Utilize an external tool, like Ensembl's Variant Effect Predictor (VEP), to validate mutation locations. Verify that annotations are accurate and correspond to expected splice site positions.
6. Revise or Reprocess Data
   If using a preloaded dataset or public data from cBioPortal, there may be inaccuracies in the original mutation annotations. Consider reannotating the mutation data using tools such as VEP or ANNOVAR.
7. Reach Out to cBioPortal Support
   If the above solutions don't resolve the issue, it could be a bug or limitation in the Mutation Mapper tool. You can:
   Submit the issue on the
   cBioPortal
   GitHub
   Issues
   page
   .
   Provide details including the gene, mutation examples, dataset format, and screenshots of the problem.
8. Consider Alternative Visualization
   If cBioPortal's Mutation Mapper continues to misrepresent splice site mutations, consider using alternative visualization tools, such as:
   Integrative Genomics Viewer (IGV) for directly mapping mutations to gene sequences.
   Custom R or Python scripts to plot mutations along gene models.