MYH2

Chr 17ADAR

myosin heavy chain 2

NCBI Gene: 4620ENSG00000125414UniProt: Q9UKX2

Myosins are actin-based motor molecules with ATPase activity essential for muscle contraction

Primary Disease Associations & Inheritance

Congenital myopathy 6 with ophthalmoplegiaMIM #605637
ADAR
697
ClinVar variants
55
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— MYH2
🧬
Gene-Disease Validity (ClinGen)
myopathy, proximal, and ophthalmoplegia · ADModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
55 Pathogenic / Likely Pathogenic· 427 VUS of 697 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.69LOEUF
pLI 0.000
Z-score 4.15
OE 0.55 (0.44–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.97Z-score
OE missense 0.82 (0.78–0.87)
826 obs / 1001.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.55 (0.44–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.78–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 53 / 97.1Missense obs/exp: 826 / 1001.7Syn Z: -0.69

ClinVar Variant Classifications

697 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic21
VUS427
Likely Benign210
Benign1
Conflicting4
34
Pathogenic
21
Likely Pathogenic
427
VUS
210
Likely Benign
1
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
0
13
0
34
Likely Pathogenic
14
1
6
0
21
VUS
4
379
38
6
427
Likely Benign
0
3
88
119
210
Benign
0
0
0
1
1
Conflicting
—4
Total39383145126697

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital myopathy 6 with ophthalmoplegia

MIM #605637

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Comprehensive bioinformatics and machine learning analyses for breast cancer staging using TCGA dataset.
Das SC et al.·Brief Bioinform
2024
Hereditary myosin myopathies.
Oldfors A·Neuromuscul Disord
2007Review
Thick filament diseases.
Oldfors A et al.·Adv Exp Med Biol
2008Review
A review of core myopathy: central core disease, multiminicore disease, dusty core disease, and core-rod myopathy.
Ogasawara M et al.·Neuromuscul Disord
2021Review
MYH2-associated myopathy caused by a novel splice-site variant.
Cassini TA et al.·Neuromuscul Disord
2023Case report
Myosinopathies: pathology and mechanisms.
Tajsharghi H et al.·Acta Neuropathol
2013Review
MYH2-associated myopathy caused by novel compound heterozygous mutations: a case report and literature review.
Kang Y et al.·J Hum Genet
2025Review
MYH2 myopathy, a new case expands the clinical and pathological spectrum of the recessive form.
Telese R et al.·Mol Genet Genomic Med
2020Case report
Novel mutation in the MYH2 gene in a symptomatic neonate with a hereditary myosin myopathy.
Oatmen K et al.·J Neonatal Perinatal Med
2022Case report
A Case of a Patient With MYH2-Associated Myopathy Presenting With a Chief Complaint of Hand Tremor.
Liao X et al.·Tremor Other Hyperkinet Mov (N Y)
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Spastic Cerebral Palsy

3D-Microscopic Muscle Architecture in Cerebral Palsy

RECRUITING
NCT06584851Universitaire Ziekenhuizen KU LeuvenStarted 2019-05-02

External Resources

Links to major genomics databases and tools