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HeartVar

HeartVar is a research tool for preliminary ACMG/AMP classification of variants found in cardiovascular disease cohorts. Given a gene, variant, and clinical context, it queries around 20 public databases in parallel and assembles the evidence into a per-criterion view. Classification is hybrid. Nineteen criteria are decided programmatically in Python from structured data; seven that require interpretation are decided by a single LLM call, which is optional and off by default.

What's in here

Entry What it is
backend/ The FastAPI service, the ACMG engine (acmg/), the per-source clients (clients/), shipped reference JSON (data/) and the test suite (tests/).
static/ Frontend CSS and JavaScript, the vendored 3Dmol viewer, and acmg_constants.json.
index.html The whole single-page frontend.
scripts/ Deploy-host tooling that builds the local data caches.
Dockerfile Runtime image. Dockerfile.builder is the data-mirror build job.
.env.example Every environment variable.

Licence and data sources

The code is MIT, see LICENSE. The data the build scripts fetch is not covered by that licence and several sources carry their own terms. The full per-source list is in scripts/README.md.

Citing this work

HeartVar: An LLM-Assisted Tool for Clinical Classification of Variants in Cardiovascular Disease Cohorts. Jamie-Lee Thompson, Debjani Das, Sally L Dunwoodie, Eleni Giannoulatou. bioRxiv 2026.09.10.750569; doi: https://doi.org/10.64898/2026.09.10.750569

Acknowledgements

Supported by Anthropic's AI for Science program. Built on public resources from Ensembl/EMBL-EBI, the Broad Institute (gnomAD, SpliceAI), Google DeepMind (AlphaMissense), NCBI (ClinVar, PubMed, PubTator3, MedGen), UniProt, EBI ProtVar, GTEx, PanelApp Australia, GenCC, the Alliance of Genome Resources/MGI, BioGRID, Open Targets, ClinGen (eRepo) and AlphaFold. The CHDgene gene list is maintained by Victor Chang Cardiac Research Institute.

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HeartVar: LLM-assisted ACMG/AMP variant curation for cardiac disease

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