Description

A multiplexed assay of variant effect (MAVE) measures what thousands of variants in a gene do to that gene's function, all in one experiment. MaveMD is a clinically curated collection inside MaveDB: score sets selected for clinical relevance, standardized, and annotated with the metadata a laboratory needs in order to judge whether an assay is fit to support a variant classification.

Score sets were selected by searching MaveDB, by finding publications cited in ClinVar for functional evidence, and by asking the genetics community, then restricted to genes with a moderate or stronger gene-disease association in ClinGen or GenCC and curated by a multidisciplinary team (McEwen et al.). Where the authors of a study, or a later reanalysis, compared the assay against variants already classified as pathogenic or benign, the resulting thresholds carry an ACMG/AMP PS3 or BS3 evidence code. Many score sets have no such calibration; those still carry the measurement and its functional class. A large share of the evidence codes shown come from calibrations MaveDB marks research use only, which is stated on each item.

This collection shows those measurements on the human genome. It covers several dozen score sets across a few dozen disease-associated genes and grows as MaveDB curates more; the date of the data shown is on each track's configuration page. Two views are available:

• MaveMD Maps draws each score set as a variant effect map, one column per amino acid position and one row per substitution. This is the view for seeing at a glance which parts of a protein tolerate change.
• MaveMD Variants draws one item per measured variant, carrying its assay score, its ACMG functional evidence code where one exists, the assay metadata, and matching ClinVar and gnomAD annotations. This is the view for looking up a single variant and for filtering.

The Maps view is a subset of the Variants view drawn differently: it can only show a variant that is a single amino acid substitution, so nucleotide-level variants outside coding sequence, insertions and deletions appear in the Variants track alone.

A broader, uncurated selection of MaveDB experiments, without clinical calibration, is in the MaveDB Experiments collection.

References

McEwen AE, Stone J, Tejura M, Gupta P, Capodanno BJ, Da EY, Grindstaff SB, Moore N, Reinhart D, Snyder AE et al. MaveMD: A functional data resource for genomic medicine. medRxiv. 2025 Nov 19;. PMID: 41332838; PMC: PMC12668102

Rubin AF, Stone J, Bianchi AH, Capodanno BJ, Da EY, Dias M, Esposito D, Frazer J, Fu Y, Grindstaff SB et al. MaveDB 2024: a curated community database with over seven million variant effects from multiplexed functional assays. Genome Biol. 2025 Jan 21;26(1):13. PMID: 39838450; PMC: PMC11753097

Arbesfeld JA, Da EY, Stevenson JS, Kuzma K, Paul A, Farris T, Capodanno BJ, Grindstaff SB, Riehle K, Saraiva-Agostinho N et al. Mapping MAVE data for use in human genomics applications. Genome Biol. 2025 Jun 25;26(1):179. PMID: 40563119; PMC: PMC12188674

Brnich SE, Abou Tayoun AN, Couch FJ, Cutting GR, Greenblatt MS, Heinen CD, Kanavy DM, Luo X, McNulty SM, Starita LM et al. Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework. Genome Med. 2019 Dec 31;12(1):3. PMID: 31892348; PMC: PMC6938631