MYOM2

Chr 8

myomesin 2

Also known as: TTNAP

NCBI Gene: 9172ENSG00000036448UniProt: P54296

MYOM2 encodes a major component of the myofibrillar M band that binds myosin, titin, and light meromyosin in muscle sarcomeres. Mutations cause hypertrophic cardiomyopathy and tetralogy of Fallot with autosomal dominant inheritance. The gene shows low constraint against loss-of-function variants, suggesting tolerance to heterozygous disruption.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
11
Pubs (1 yr)
81
P/LP submissions
0%
P/LP missense
1.48
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— MYOM2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
81 unique Pathogenic / Likely Pathogenic· 312 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.48LOEUF
pLI 0.000
Z-score -2.37
OE 1.27 (1.09–1.48)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-5.30Z-score
OE missense 1.50 (1.43–1.56)
1356 obs / 906.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.27 (1.09–1.48)
0≤0.351.4
Missense OE1.50 (1.43–1.56)
0≤0.61.4
Synonymous OE1.42
0≤1.21.6
LoF obs/exp: 114 / 89.8Missense obs/exp: 1356 / 906.8Syn Z: -6.40
DN
0.6744th %ile
GOF
0.6737th %ile
LOF
0.4430th %ile

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.

DNprediction above median
GOFprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic75
Likely Pathogenic6
VUS312
Likely Benign37
Benign43
Conflicting1
75
Pathogenic
6
Likely Pathogenic
312
VUS
37
Likely Benign
43
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
75
0
75
Likely Pathogenic
0
0
6
0
6
VUS
0
290
22
0
312
Likely Benign
0
14
10
13
37
Benign
0
19
6
18
43
Conflicting
—1
Total032311931474

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MYOM2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients