MYH2
Chr 17ADARmyosin heavy chain 2
Also known as: CMYO6, CMYP6, IBM3, MYH2A, MYHSA2, MYHas8, MyHC-2A, MyHC-IIa
The MYH2 gene encodes a class II myosin heavy chain that functions as an actin-based motor protein essential for skeletal muscle contraction. Mutations cause congenital myopathy 6 with ophthalmoplegia through a dominant-negative mechanism, inherited in both autosomal dominant and autosomal recessive patterns. The protein localizes to myofibrils in the cytoplasm and is part of heterohexameric muscle myosin complexes that generate mechanical force for muscle function.
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. 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.
ClinVar Variant Classifications
200 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 | 5 | 0 | 1 | 0 | 6 |
Likely Pathogenic | 9 | 0 | 0 | 0 | 9 |
VUS | 1 | 105 | 6 | 0 | 112 |
Likely Benign | 0 | 0 | 26 | 40 | 66 |
Benign | 0 | 0 | 0 | 1 | 1 |
Conflicting | — | 6 | |||
| Total | 15 | 105 | 33 | 41 | 200 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
MYH2 · 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
External Resources
Links to major genomics databases and tools