MYH8

myosin heavy chain 8, the group of Myosin heavy chains, class II

Basic information

Region (hg38): 17:10390322-10421950

Links

ENSG00000133020 ∙ NCBI:4626 ∙ OMIM:160741 ∙ HGNC:7578 ∙ Uniprot:P13535 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• trismus-pseudocamptodactyly syndrome (Limited), mode of inheritance: AD
• trismus-pseudocamptodactyly syndrome (Supportive), mode of inheritance: AD
• Carney complex - trismus - pseudocamptodactyly syndrome (Limited), mode of inheritance: AD
• trismus-pseudocamptodactyly syndrome (Limited), mode of inheritance: AD
• trismus-pseudocamptodactyly syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Carney complex variant; Arthrogryposis, distal, type 7 (Trismus-pseudocamptodactyly syndrome)	AD	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	Craniofacial; Musculoskeletal	4443857; 4837286; 12800911; 15590965; 15282353; 17041932; 18049072; 20949528
In one family, cardiac and dermatologic findings appeared to co-segregate with the disease

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYH8 gene.

• Carney complex - trismus - pseudocamptodactyly syndrome (1 variants)
• not provided (1 variants)
• Hecht syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYH8 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			18	24	15	57
missense	1		157	15	7	180
nonsense			7		1	8
start loss						0
frameshift			6			6
inframe indel						0
splice donor/acceptor (+/-2bp)			3	1		4
splice region			7	7	1	15
non coding			8	21	35	64
Total	1	0	199	61	58

Highest pathogenic variant AF is 0.0000132

Variants in MYH8

This is a list of pathogenic ClinVar variants found in the MYH8 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-10390378-C-G		Hecht syndrome	Likely benign (Sep 04, 2019)
17-10390382-A-G		Hecht syndrome	Likely benign (Oct 28, 2019)
17-10390421-C-G		Hecht syndrome	Uncertain significance (Jan 13, 2018)
17-10390435-T-C		Hecht syndrome	Uncertain significance (Jan 13, 2018)
17-10390479-A-C			Uncertain significance (Jun 06, 2018)
17-10390525-T-C		13 conditions	Uncertain significance (-)
17-10390532-C-G		Hecht syndrome	Uncertain significance (Jan 12, 2018)
17-10390540-C-T		not specified	Uncertain significance (Jun 03, 2022)
17-10390569-C-T		not specified	Uncertain significance (Dec 11, 2023)
17-10390603-C-G		Hecht syndrome	Uncertain significance (Jul 16, 2023)
17-10391659-G-A			Benign (Nov 12, 2018)
17-10391910-T-A		not specified	Uncertain significance (Jan 23, 2023)
17-10391917-T-C		not specified	Uncertain significance (May 17, 2023)
17-10391923-G-A			Uncertain significance (Mar 23, 2017)
17-10391959-T-A		not specified	Uncertain significance (Jun 27, 2022)
17-10391974-C-G		not specified	Uncertain significance (Nov 21, 2022)
17-10392180-C-T			Benign (Nov 12, 2018)
17-10392303-C-T			Benign (Dec 08, 2019)
17-10392304-CA-C			Benign (Oct 28, 2019)
17-10392567-C-T		Hecht syndrome	Uncertain significance (Jan 13, 2018)
17-10392571-C-T		Hecht syndrome • not specified	Conflicting classifications of pathogenicity (Jun 05, 2023)
17-10392572-A-T		not specified	Uncertain significance (Feb 16, 2023)
17-10392579-C-T		not specified	Uncertain significance (May 03, 2023)
17-10392597-T-G		Hecht syndrome • MYH8-related disorder • not specified	Benign/Likely benign (Aug 01, 2024)
17-10392602-A-G		MYH8-related disorder	Benign (Oct 17, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYH8	protein_coding	protein_coding	ENST00000403437	38	31629

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.05e-51	0.00000823	124610	4	1134	125748	0.00454

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.350	965	996	0.969	0.0000595	12871
Missense in Polyphen		357	361.73	0.98692		4950
Synonymous	-0.682	399	382	1.04	0.0000228	3509
Loss of Function	1.30	86	100	0.860	0.00000532	1282

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0147	0.0146
Ashkenazi Jewish	0.00368	0.00368
East Asian	0.0120	0.0120
Finnish	0.00263	0.00259
European (Non-Finnish)	0.00373	0.00373
Middle Eastern	0.0120	0.0120
South Asian	0.00337	0.00330
Other	0.00391	0.00392

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Muscle contraction.
• Disease: DISEASE: Carney complex variant (CACOV) [MIM:608837]: Carney complex is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas. Familial cardiac myxomas are associated with spotty pigmentation of the skin and other phenotypes, including primary pigmented nodular adrenocortical dysplasia, extracardiac (frequently cutaneous) myxomas, schwannomas, and pituitary, thyroid, testicular, bone, ovarian, and breast tumors. Cardiac myxomas do not develop in all patients with the Carney complex, but affected patients have at least two features of the complex or one feature and a clinically significant family history. {ECO:0000269|PubMed:15282353}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Arthrogryposis, distal, 7 (DA7) [MIM:158300]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA7 is characterized by an inability to open the mouth fully (trismus) and pseudocamptodactyly in which wrist dorsiflexion, but not volarflexion, produces involuntary flexion contracture of distal and proximal interphalangeal joints. Additional features include shortened hamstring muscles and short stature. {ECO:0000269|PubMed:15282353, ECO:0000269|PubMed:20949528}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tight junction - Homo sapiens (human);Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

• pRec: 0.187

Intolerance Scores

• loftool: 0.139
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.27

Haploinsufficiency Scores

• pHI: 0.491
• hipred: N
• hipred_score: 0.443
• ghis: 0.412

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.214

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myh8

Gene ontology

• Biological process: skeletal muscle contraction;protein dephosphorylation;muscle contraction;muscle filament sliding;ATP metabolic process
• Cellular component: cytoplasm;cytosol;muscle myosin complex;sarcomere;myosin filament
• Molecular function: microfilament motor activity;calmodulin binding;ATP binding;structural constituent of muscle;ATPase activity;myosin phosphatase activity;myosin light chain binding;actin filament binding