MYH7

Chr 14ADDigenic dominantAR

myosin heavy chain 7

Also known as: CMD1S, CMH1, CMYO7A, CMYO7B, CMYP7A, CMYP7B, MPD1, MYHCB

NCBI Gene: 4625 ENSG00000092054 UniProt: P12883

Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 1SMIM #613426

Cardiomyopathy, hypertrophic, 1MIM #192600

ADDigenic dominant

Congenital myopathy 7A, myosin storage, autosomal dominantMIM #608358

Congenital myopathy 7B, myosin storage, autosomal recessiveMIM #255160

Laing distal myopathyMIM #160500

Left ventricular noncompaction 5MIM #613426

UniProtCardiomyopathy, familial hypertrophic, 1

UniProtMyopathy, distal, 1

5861

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— MYH7

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

20 Pathogenic / Likely Pathogenic· 254 VUS of 5861 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

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.

0.57LOEUF

pLI 0.000

Z-score 5.05

OE 0.45 (0.35–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

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.

3.93Z-score

OE missense 0.67 (0.63–0.71)

742 obs / 1110.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

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.0.45 (0.35–0.57)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.63–0.71)

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.1.17

0≤1.21.6

LoF obs/exp: 43 / 96.5Missense obs/exp: 742 / 1110.9Syn Z: -2.91

ClinVar Variant Classifications

5861 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic19

VUS254

Likely Benign118

Conflicting1

Pathogenic

Likely Pathogenic

254

VUS

118

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	2	17	0	0	19
VUS	15	213	24	2	254
Likely Benign	0	4	39	75	118
Benign	0	0	0	0	0
Conflicting	—				1
Total	17	235	63	77	393

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

View in ClinVar →

Protein Context — Lollipop Plot

MYH7 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MYH7-related arrhythmogenic right ventricular cardiomyopathy

limited

ADUndeterminedUncertain

Cardiac

G2P ↗

MYH7-related hypertrophic cardiomyopathy

definitive

ADUndeterminedAltered Gene Product Structure

Cardiac

G2P ↗

missense variantinframe deletionstop gained NMD escaping

MYH7-related dilated cardiomyopathy

definitive

ADUndeterminedAltered Gene Product Structure

Cardiac

G2P ↗

missense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

MYOSIN, HEAVY CHAIN 7, CARDIAC MUSCLE, BETA; MYH7

MIM #160760 · *

Cardiomyopathy, dilated, 1S

MIM #613426