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MaveMD: A functional data resource for genomic medicine

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McEwen, Abbye E., Stone, Jeremy, Tejura, Malvika, Gupta, Pankhuri, Capodanno, Benjamin J., Da, Estelle Y., Grindstaff, Sally B., Moore, Nick +6 more·2025·Genome Medicine
DOI 10.1101/2025.11.15.25336228PMC PMC12668102
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Abstract

Variants of uncertain significance (VUS) undermine genetic medicine implementation because they have an unknown relationship to disease and cannot be used for clinical decision-making. While evidence from multiplexed assays of variant effect (MAVEs) can help resolve VUS, major barriers prevent routine clinical use, including data fragmentation and assay calibration. To address these challenges, we present MaveMD (MAVEs for MeDicine), a new interface for the MaveDB database that displays clinical evidence calibrations, provides intuitive visualizations, integrates with ClinVar and ClinGen, and exports clinical evidence compatible with ACMG/AMP guidelines. MaveMD currently contains 476,076 variant effect measurements curated from 82 MAVE datasets spanning 39 disease-associated genes, enabling classification of 75% of ClinVar VUS and 62% of future variants in these genes. MaveMD is designed to support and facilitate future data generation efforts and the use of MAVE evidence in clinical practice, thereby reducing the VUS burden and improving genetic medicine outcomes.

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  • MaveDB has recently been developed further for translational purposes with the release of a clinical layer, MaveMD, which transforms MAVE functional scores into calibrated ACMG-compatible evidence that clinicians can use to support variant classification.

    “MaveDB has recently been developed further for translational purposes with the release of a clinical layer of the database – MaveMD – which transforms MAVE functional scores into calibrated ACMG-compatible evidence that clinicians can use to support variant classification (104).”

    From Massively parallel functional genomic assays in endocrinology: from promise to delivery (2026) · cites this paper as [104]

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Cited by

Sorted by citations

Authors
McEwen, A. E., Stone, J., Tejura, M., Gupta, P., Capodanno, B. J., Da, E. Y., Grindstaff, S. B., Moore, N., Reinhart, D., Snyder, A. E., Stergachis, A. B., Starita, L. M., Fowler, D. M., & Rubin, A. F.
Affiliations
  • University of Washington (US)
  • Walter and Eliza Hall Institute of Medical Research (AU)
  • The University of Melbourne (AU)
Corresponding author
Rubin, Alan F.
ORCID
Venue
Genome Medicine
Publisher
openRxiv
Published
2025-11-19
ISSN
1756-994X (ISSN-L)
DOI
10.1101/2025.11.15.25336228
PMC
PMC12668102
OpenAlex
W7214729282
Cited by
5
References
1
Citations by year
2026: 5
FWCI
16.13
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome Medicine (publishedVersion, cc-by)
  • medRxiv (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Burroughs Wellcome Fund
  • Pew Charitable Trusts
  • Alex's Lemonade Stand Foundation for Childhood Cancer
  • Warren Alpert Foundation (WAF-CLEP- PD 10089501-01)
  • National Institutes of Health
  • National Human Genome Research Institute (UM1HG011969, R01HG013025)
  • Medical Research Future Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
variants of uncertain significance, MAVE, MaveDB, variant effect prediction, clinical variant interpretation, genomic medicine, disease-associated genes, variant interpretation

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