MYH1

protein-coding

myosin heavy chain 1, the group of Myosin heavy chains, class II

Gene summary

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]

MANE transcript

NM_005963.4

Inheritance

ClinVar variants

U:305B:21

Top phenotype

MYH1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr17:10,492,307-10,518,542

External References & Databases

Ensembl (ENSG00000109061)

Transcript & Mutation Effects

hg38 • Region Span ~26.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

rhabdomyolysisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005290

Submitter: PanelApp Australia

hereditary skeletal muscle disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700223

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYH1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 295

MYH1-related disorderTotal: 16

not providedTotal: 15

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005963.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	7 clinvar		9
missense			301 clinvar	11 clinvar		312
nonsense				1 clinvar		1
start loss						0
frameshift				2 clinvar		2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	305	21	0	326

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005963.4	RefSeq	NP_005954.3	38	MANE Select
ENST00000226207.6	Ensembl	ENSP00000226207.5	38	MANE Select
ENST00000958695.1	Ensembl	ENSP00000628754.1	38	Standard
ENST00000958695.2	Ensembl	ENSP00000628754.1	38	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)

Biological Process

muscle contraction

Molecular Function

motor activity
protein binding
calmodulin binding
ATP binding
actin filament binding

Cellular Component

muscle myosin complex
intercalated disc
A band
myosin filament
cytoplasmic ribonucleoprotein granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000226207
Coding exons: 38
Length: 26237
Individuals with no LoFs: 123638
Homozygous LoFs: 15
Heterozygous LoFs: 2095
Defined: 125748
p: 0.00843

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0357	1027	1.03e+3	0.997	0.0000576	12939
Missense (PolyPhen)		376	391.65	0.96003		5226
Synonymous	-1.73	424	381	1.11	0.0000208	3497
Loss of Function	0.850	91	100	0.908	0.00000528	1234

Population LoF Frequency

Population	CAF	p-value	Status
African	0.017	0.017	notable
Latino/Admixed American	0.020	0.020	notable
Ashkenazi Jewish	0.0099	0.010	notable
East Asian	0.014	0.014	notable
Finnish	0.0084	0.0083	notable
European (Non-Finnish)	0.0038	0.0038	notable
South Asian	0.0052	0.0051	notable
Other	0.0070	0.0069	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Muscle contraction.;

Recessive Scores

pRec: 0.306

Intolerance Scores

LoFtool: 0.126
RVIS EVS: -1.08
RVIS percentile EVS: 7.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.765

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium