MYH2

myosin heavy chain 2, the group of Myosin heavy chains, class II

Basic information

Region (hg38): 17:10521148-10549700

Previous symbols: [ "IBM3" ]

Links

ENSG00000125414 ∙ NCBI:4620 ∙ OMIM:160740 ∙ HGNC:7572 ∙ Uniprot:Q9UKX2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myopathy, proximal, and ophthalmoplegia (Strong), mode of inheritance: Semidominant
• hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome (Supportive), mode of inheritance: AD
• childhood-onset autosomal recessive myopathy with external ophthalmoplegia (Supportive), mode of inheritance: AR
• myopathy, proximal, and ophthalmoplegia (Strong), mode of inheritance: AR
• myopathy, proximal, and ophthalmoplegia (Strong), mode of inheritance: AR
• myopathy, proximal, and ophthalmoplegia (Strong), mode of inheritance: AD
• hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome (Limited), mode of inheritance: AD
• myopathy, proximal, and ophthalmoplegia (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital myopathy 6 with ophthalmoplegia	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	11114175; 24193343

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYH2 gene.

• Myopathy, proximal, and ophthalmoplegia (39 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYH2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			14	243	10	267
missense		2	639	9		650
nonsense	17	5	1			23
start loss			1			1
frameshift	21	5	3			29
inframe indel			11			11
splice donor/acceptor (+/-2bp)	2	20	1			23
splice region			36	37		73
non coding			15	117	53	185
Total	40	32	685	369	63

Highest pathogenic variant AF is 0.000158

Variants in MYH2

This is a list of pathogenic ClinVar variants found in the MYH2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-10521149-A-G		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Jan 13, 2018)
17-10521229-G-T		Myopathy, proximal, and ophthalmoplegia	Benign/Likely benign (Aug 25, 2018)
17-10521286-T-C		Myopathy, proximal, and ophthalmoplegia	Conflicting classifications of pathogenicity (Nov 20, 2023)
17-10521301-T-A		MYH2-related disorder	Likely benign (Jul 22, 2020)
17-10521305-T-G		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Oct 10, 2023)
17-10521314-C-T		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Dec 03, 2023)
17-10521315-G-A		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Nov 08, 2023)
17-10521320-T-C		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Jul 22, 2019)
17-10521326-C-T		not specified • Myopathy, proximal, and ophthalmoplegia • MYH2-related disorder	Benign/Likely benign (Aug 01, 2024)
17-10521327-G-T		Myopathy, proximal, and ophthalmoplegia	Likely benign (Oct 29, 2021)
17-10521329-A-C		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Aug 24, 2023)
17-10521334-G-A		Myopathy, proximal, and ophthalmoplegia	Likely benign (Oct 09, 2023)
17-10521341-T-C		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Nov 14, 2022)
17-10521351-C-T		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Sep 02, 2020)
17-10521353-A-G		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Oct 27, 2022)
17-10521356-T-C		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Jan 29, 2024)
17-10521357-C-T			Uncertain significance (May 08, 2020)
17-10521358-A-G		Myopathy, proximal, and ophthalmoplegia	Likely benign (Dec 01, 2023)
17-10521362-C-T		Myopathy, proximal, and ophthalmoplegia • Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
17-10521363-G-A		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Oct 03, 2023)
17-10521369-C-T		Myopathy, proximal, and ophthalmoplegia • Inborn genetic diseases	Uncertain significance (Jun 07, 2024)
17-10521370-G-A		Myopathy, proximal, and ophthalmoplegia	Likely benign (Jun 17, 2022)
17-10521398-C-T		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Dec 23, 2023)
17-10521399-G-A		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (May 28, 2022)
17-10521416-G-C		Myopathy, proximal, and ophthalmoplegia	Uncertain significance (Jun 25, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYH2	protein_coding	protein_coding	ENST00000245503	38	28810

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.67e-23	1.00	125566	0	182	125748	0.000724

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.97	826	1.00e+3	0.825	0.0000599	12909
Missense in Polyphen		254	325.4	0.78059		4458
Synonymous	-0.693	404	387	1.04	0.0000228	3539
Loss of Function	4.15	53	97.1	0.546	0.00000527	1244

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00123	0.00123
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000707	0.000707
Finnish	0.00171	0.00171
European (Non-Finnish)	0.000591	0.000571
Middle Eastern	0.000707	0.000707
South Asian	0.000882	0.000882
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Muscle contraction. Required for cytoskeleton organization (By similarity). {ECO:0000250}.
• Disease: DISEASE: Myopathy, proximal, and ophthalmoplegia (MYPOP) [MIM:605637]: A muscular disorder characterized by mild-to- moderate muscle weakness, ophthalmoplegia, and contractures at birth in some patients. Muscle biopsies from patients show predominance of type 1 fibers and small or absent type 2A fibers. The disease is non-progressive or it progresses very slowly. Inheritance is autosomal dominant or recessive. {ECO:0000269|PubMed:11114175}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tight junction - Homo sapiens (human);amb2 Integrin signaling;Alpha4 beta1 integrin signaling events (Consensus)

Recessive Scores

• pRec: 0.231

Intolerance Scores

• loftool: 0.0360
• rvis_EVS: -2.09
• rvis_percentile_EVS: 1.57

Haploinsufficiency Scores

• pHI: 0.892
• hipred: Y
• hipred_score: 0.632
• ghis: 0.523

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.611

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myh2

Gene ontology

• Biological process: muscle contraction;muscle filament sliding;Fc-gamma receptor signaling pathway involved in phagocytosis
• Cellular component: cytosol;muscle myosin complex;myofibril;sarcomere;myosin filament;protein-containing complex
• Molecular function: microfilament motor activity;protein binding;calmodulin binding;ATP binding;actin filament binding