MYH8

Chr 17AD

myosin heavy chain 8

Also known as: DA7, MyHC-peri, MyHC-pn, gtMHC-F

The MYH8 protein is a myosin heavy chain that functions in skeletal muscle contraction and is predominantly expressed in fetal skeletal muscle. Mutations cause trismus-pseudocamptodactyly syndrome and Carney complex variant, both inherited in an autosomal dominant pattern. The gene shows very low constraint against loss-of-function variants (pLI near zero), suggesting the pathogenic variants likely affect muscle function through other mechanisms.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 1.032 OMIM phenotypes
Clinical SummaryMYH8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 357 VUS of 500 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.30
OE 0.86 (0.721.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.35Z-score
OE missense 0.97 (0.921.02)
965 obs / 996.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.86 (0.721.03)
00.351.4
Missense OE0.97 (0.921.02)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 86 / 100.0Missense obs/exp: 965 / 996.0Syn Z: -0.68
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedMYH8-related Carney complex variantOTHERAD
strongMYH8-related Trismus-pseudocamptodactyly syndromeLOFAD
DN
0.82top 10%
GOF
0.6151th %ile
LOF
0.3358th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS357
Likely Benign62
Benign44
Conflicting24
8
Pathogenic
2
Likely Pathogenic
357
VUS
62
Likely Benign
44
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
2
0
0
0
2
VUS
14
294
29
20
357
Likely Benign
1
14
25
22
62
Benign
0
2
34
8
44
Conflicting
24
Total173109650497

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

View in ClinVar →

Protein Context — Lollipop Plot

MYH8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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