824df26b6320b692d629566c5a10b15004da82ce lrnassar Tue Sep 29 16:09:00 2026 -0700 addProteinSequence in mavemdLib translates each transcript's CDS from hg38.2bit so makeMaveMdVariants can check every projected codon against the reference residue its own HGVS term asserts; the existing comparison against MaveDB's genomic mapping only reaches the 3% of projected items that carry both terms, because 18 of the 40 protein accessions have no genomic-route variants at all. 39 of 40 accessions match at 0.000%; NP_689629.2 (FKRP) has 99 nonsense terms numbered one codon downstream of their own reference residue, which still reach mavemdVar through MaveDB's genomic mapping but are dropped from mavemdMap, which places columns from the protein term and has no fallback. The haplotype test now also reads hgvs_nt, since PTEN 00000054-a-1 states 1,236 haplotypes as c.[1207G>T;1209C>T] with no protein term and they were counted as rejected submissions, making both figures in the makeDoc wrong. assayLine runs the heatmap legend through asciiText because bedField turns the en dash in three MaveDB titles into – and the legend is drawn as raster text; clinGenId links to by_canonicalid rather than /allele, which serves JSON to a browser, matching human/civic.ra; the generated filter fragment no longer emits the blank line after each group that the makeDoc itself warns ends a stanza; and runBuild.sh tails the log on failure instead of dying silently under set -e. Also reworded the grey legend entry, which said no threshold was reached in either direction but covers 6,656 normal and 145 abnormal items, alphabetized the references, and fixed stale counts in the makeDoc. Caught by Claude review of 29af14b, fcf788d and 97c7de5. refs #38407 refs #37800 diff --git src/hg/makeDb/trackDb/human/hg38/mavemd.html src/hg/makeDb/trackDb/human/hg38/mavemd.html index 73cc6e51e0f..5ad6749374a 100644 --- src/hg/makeDb/trackDb/human/hg38/mavemd.html +++ src/hg/makeDb/trackDb/human/hg38/mavemd.html @@ -1,93 +1,92 @@

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 +multidisciplinary team (McEwen et al., 2025). 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

+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 +