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REST VariantValidator2 SHAIP

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VariantValidator SHAIP is a high‑performance FastAPI-based interface to the VariantValidator framework, providing scalable genomic variant validation, formatting, and transcript mapping via a modern REST API.

Overview

VariantValidator SHAIP is designed to support high-throughput and automated workflows requiring accurate interpretation of genetic variant descriptions.

The service builds upon the VariantValidator engine while introducing a modernised API layer optimised for containerised environments and batch processing pipelines.

Key capabilities include:

  • Validation of variant descriptions using HGVS nomenclature
  • Genomic to transcript and protein mapping
  • Support for multiple input formats (HGVS, VCF, pseudo-VCF)
  • Compatibility with existing VariantValidator workflows
  • Efficient batch processing for pipeline integration

About VariantValidator

VariantValidator is a software toolkit developed to validate and interpret sequence variant descriptions according to the HGVS nomenclature standard.

It provides:

  • Syntax validation and correction of HGVS expressions
  • Mapping between genomic, transcript, and protein representations
  • Support for RefSeq and Ensembl transcript sets
  • Accurate handling of discrepancies between reference sequences

Further information is available at:

Support is available via our support page

Available Endpoints

VariantValidator SHAIP provides the following endpoints:

  • variantformatter-v2
    High-performance genomic → transcript → protein formatter Replaces the LOVD endpoint and VariantFormatter endpoint

  • variantvalidator
    Full HGVS validation using the RefSeq transcript set

  • variantvalidator-ensembl
    Full HGVS validation using the Ensembl transcript set

  • gene2transcripts-v2
    Gene to transcript resolution

  • hgvs2reference
    Reference sequence extraction from HGVS

  • versions
    Software and dataset version reporting

  • keep-alive
    Service health check

Detailed endpoint usage is described in the Endpoints section.

When to Use Each Endpoint

  • Use variantformatter-v2 for high-throughput genomic or VCF-like inputs
  • Use variantvalidator for full HGVS validation (RefSeq)
  • Use variantvalidator-ensembl for Ensembl-based workflows
  • Use gene2transcripts-v2 to identify valid transcripts for a gene
  • Use hgvs2reference to retrieve reference sequence only

Technology Stack

The service is built using:

  • FastAPI
  • Python 3.12
  • VariantValidator
  • VariantFormatter
  • vv_hgvs
  • SeqRepo
  • vvseqrepo (sequence database backend)
  • vvta (transcript annotation database)
  • Docker

Users interact with the API via HTTP and do not need to manage these components directly.

Documentation Structure

This documentation is organised as follows:

  • Getting Started
    Minimal usage guidance and entry points

  • Endpoints
    Detailed API endpoint documentation

  • Transcript Selection
    Transcript filtering strategies and behaviour

  • Performance
    Guidance for optimising throughput and response size

  • Docker
    Deployment and runtime environment configuration

Performance Overview

Performance is influenced primarily by:

  • Transcript selection strategy
  • Use of liftover
  • Volume of transcripts returned
  • Inclusion of auxiliary data (e.g. exon structures)

For optimal performance:

  • Prefer mane_select, mane, or explicit transcript IDs
  • Avoid all and raw unless required
  • Disable liftover where not needed

Detailed guidance is provided in the Performance section.

Usage Context

VariantValidator SHAIP is intended for:

  • Bioinformatics pipelines
  • Clinical variant interpretation workflows
  • Research applications requiring HGVS standardisation
  • High-throughput genomic variant processing

Disclaimer

This software is intended for research and bioinformatics workflows.

  • It does not provide clinical diagnoses
  • Outputs may change as reference datasets are updated
  • Users are responsible for interpretation and downstream use

Clinical decisions should be made in consultation with qualified professionals.

By using this software you accept our terms and conditions of use

Citation

If using VariantValidator in published work, please cite:

Freeman, P. J., Hart, R. K., Gretton, L. J., Brookes, A. J., & Dalgleish, R. (2018).
VariantValidator: Accurate validation, mapping and formatting of sequence variation descriptions.
Human Mutation, 39, 61–68. https://doi.org/10.1002/humu.23348

Freeman, P. J., Wagstaff, J. F., Fokkema, I. F. A. C., et al. (2024).
Standardizing variant naming in literature with VariantValidator to increase diagnostic rates.
Nature Genetics, 56, 2284–2286. https://doi.org/10.1038/s41588-024-01938-w