MYOM2

protein-coding

myomesin 2, the group of I-set domain containing|Myosin binding proteins|MicroRNA protein coding host genes

Gene summary

The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD and 165 kD. The predicted MYOM2 protein contains 1,465 amino acids. Like MYOM1, MYOM2 has a unique N-terminal domain followed by 12 repeat domains with strong homology to either fibronectin type III or immunoglobulin C2 domains. Protein sequence comparisons suggested that the MYOM2 protein and bovine M protein are identical. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003970.4

Inheritance

—

ClinVar variants

P:1U:412B:88

Top phenotype

MYOM2-related disorder

gnomAD constraint

pLI —, LoF o/e 1.27

Max pathogenic AF

—

Genomic locus

chr8:2,045,046-2,165,552

External References & Databases

Ensembl (ENSG00000036448)

Transcript & Mutation Effects

hg38 • Region Span ~120.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYOM2 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 406

MYOM2-related disorderTotal: 87

not providedTotal: 22

Flexion contractureTotal: 2

Sudden cardiac deathTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003970.4. 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			3 clinvar	23 clinvar	22 clinvar	48
missense			404 clinvar	25 clinvar	17 clinvar	446
nonsense		1 clinvar	1 clinvar	1 clinvar		3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	1	412	49	39	501

Highest pathogenic variant AF is 0.0000013733905

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 79 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003970.4	RefSeq	NP_003961.3	36	MANE Select
ENST00000262113.9	Ensembl	ENSP00000262113.4	36	MANE Select
ENST00000523438.1	Ensembl	ENSP00000428396.1	23	Standard
ENST00000523438.2	Ensembl	ENSP00000428396.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

extraocular skeletal muscle development
muscle contraction
skeletal muscle thin filament assembly
skeletal muscle myosin thick filament assembly
sarcomere organization

Molecular Function

protein binding
structural constituent of muscle
kinase binding
actin filament binding
muscle alpha-actinin binding

Cellular Component

mitochondrion
striated muscle thin filament
sarcomere
Z disc
M band

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000262113
Coding exons: 36
Length: 120321
Individuals with no LoFs: 124812
Homozygous LoFs: 3
Heterozygous LoFs: 933
Defined: 125748
p: 0.00373

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-5.30	1356	907	1.50	0.0000578	9579
Missense (PolyPhen)		495	342.24	1.4463		3407
Synonymous	-6.40	540	381	1.42	0.0000289	2756
Loss of Function	-2.37	114	89.8	1.27	0.00000510	972

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0023	0.0023	notable
Latino/Admixed American	0.0047	0.0047	notable
Ashkenazi Jewish	0.0073	0.0074	notable
East Asian	0.011	0.011	notable
Finnish	0.00056	0.00055	rare
European (Non-Finnish)	0.0029	0.0029	notable
South Asian	0.0028	0.0028	notable
Other	0.0046	0.0046	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Major component of the vertebrate myofibrillar M band. Binds myosin, titin, and light meromyosin. This binding is dose dependent.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.981
RVIS EVS: -0.5
RVIS percentile EVS: 21.84

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.802

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High