MYH10
Chr 17myosin heavy chain 10
Also known as: NMMHC-IIB, NMMHCB
This protein is a cellular myosin that functions in cytokinesis, cell shape maintenance, and cytoskeletal reorganization during cell spreading. Mutations cause autosomal dominant May-Hegglin anomaly and related macrothrombocytopenia syndromes characterized by bleeding disorders due to large platelets and low platelet counts. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be severe.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Extremely missense-constrained (top ~0.01%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). The Badonyi & Marsh model scores dominant-negative highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
381 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 2 | 2 | 11 | 0 | 15 |
Likely Pathogenic | 3 | 6 | 0 | 0 | 9 |
VUS | 19 | 255 | 7 | 1 | 282 |
Likely Benign | 0 | 5 | 8 | 13 | 26 |
Benign | 0 | 3 | 5 | 8 | 16 |
Conflicting | — | 1 | |||
| Total | 24 | 271 | 31 | 22 | 349 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MYH10 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools