Data

MetaDome does not host data files itself. Everything below is deposited on Zenodo under CC BY 4.0, where each record carries checksums and a full description of its contents. The prebuild pipelines, the platform and the analysis scripts are in the MetaDome GitHub repository.

Current release

MetaDome 2027, built from GENCODE v45 for GRCh38 and v19 for GRCh37, UniProtKB/Swiss-Prot 2025_01, Pfam 37.4, gnomAD v4.1 for GRCh38 and r2.0.2 for GRCh37, and ClinVar 2025-10-06. Both records below come from this build, and the code that produced them is tagged 2.0.1 in the repository.

MetaDome 2027 data release

For GRCh38 and GRCh37, this record holds the mapping databases that link every coding genomic position to a transcript, a Swiss-Prot residue and a Pfam domain consensus position; the per-residue dataset that carries the tolerance scores and the variant counts; the prebuilt visualisations and meta-domains that the platform serves; and genome-browser tracks for Pfam domain coverage, the tolerance landscape and meta-domain ClinVar evidence.

Wiel, L., & Ferraro, F. (2026). MetaDome 2027: a comprehensively updated resource for aggregating missense variant evidence across homologous human protein domains (Version 2.0) [Dataset]. Zenodo. https://doi.org/10.5281/zenodo.19376150

ClinVar variants of uncertain significance with homologous pathogenic evidence

The candidate sets behind the meta-domain evidence analysis in the MetaDome 2027 paper, published there as Supplementary Data S2 and S3, covering GRCh38.p14 and GRCh37.p13, and produced from the files in the record above. Each row is one ClinVar missense variant of uncertain significance at one Pfam domain placement where pathogenic variation is observed at the equivalent position in a homologous domain elsewhere in the genome, together with the supporting and contradicting ClinVar records at that position. More than 50,000 such variants carry that evidence without any pathogenic variant at their own codon, which is where a meta-domain contributes evidence that is otherwise unavailable.

Wiel, L. (2026). MetaDome 2027: ClinVar variants of uncertain significance at homologous Pfam domain positions (Version 1.0) [Dataset]. Zenodo. https://doi.org/10.5281/zenodo.23053554

Previous releases

MetaDome 2019 data release

Version 1.0.1, GRCh37 only, built from GENCODE v19 (GRCh37.p13), UniProtKB/Swiss-Prot 2016_09, Pfam 30.0, gnomAD r2.0.2 and ClinVar 2018-05-03. The code is tagged 1.0.1 in the repository.

Wiel, L., Baakman, C., Gilissen, D., Veltman, J. A., Vriend, G., & Gilissen, C. (2019). MetaDome: Pathogenicity analysis of genetic variants through aggregation of homologous human protein domains. https://doi.org/10.1002/humu.23798