MYH1

Chr 17

myosin heavy chain 1

Also known as: HEL71, MYHSA1, MYHa, MyHC-2X/D, MyHC-2x

NCBI Gene: 4619 ENSG00000109061 UniProt: P12882 OMIM: 160730

Myosin heavy chain 1 is a contractile protein that converts chemical energy into mechanical energy through ATP hydrolysis and is required for normal hearing by regulating outer hair cell electromotility in the cochlea. Mutations cause autosomal dominant hearing loss disorders. This gene shows extremely high constraint against loss-of-function variants, indicating that such mutations are typically not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Myosin is a major contractile protein which converts chemical energy into mechanical energy through the hydrolysis of ATP. Myosin is a hexameric protein composed of a pair of myosin heavy chains (MYH) and two pairs of nonidentical light chains. Myosin heavy chains are encoded by a multigene family. In mammals at least 10 different myosin heavy chain (MYH) isoforms have been described from striated, smooth, and nonmuscle cells. These isoforms show expression that is spatially and temporally regulated during development. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.08

Clinical Summary— MYH1

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

296 VUS of 315 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?

1.08LOEUF

pLI 0.000

Z-score 0.85

OE 0.91 (0.77–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.04Z-score

OE missense 1.00 (0.95–1.05)

1027 obs / 1030.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.91 (0.77–1.08)

0≤0.351.4

Missense OE?1.00 (0.95–1.05)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 91 / 100.2Missense obs/exp: 1027 / 1030.2Syn Z: -1.73

This gene — mechanism propensity

0.82top 10%

GOF

0.6444th %ile

LOF

0.3356th %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

315 submitted variants in ClinVar

ClinVar

Classification Summary

VUS296

Likely Benign10

Benign1

Conflicting1

296

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	293	1	2	296
Likely Benign	1	5	1	3	10
Benign	0	0	0	1	1
Conflicting	—				1
Total	1	298	2	6	308

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap MYH1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →