MYOT

myotilin, the group of I-set domain containing

Basic information

Region (hg38): 5:137867858-137887851

Previous symbols: [ "TTID", "LGMD1A", "LGMD1" ]

Links

ENSG00000120729 ∙ NCBI:9499 ∙ OMIM:604103 ∙ HGNC:12399 ∙ Uniprot:Q9UBF9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spheroid body myopathy (Supportive), mode of inheritance: AD
• myofibrillar myopathy 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myopathy, myofibrillar, 3	AD	Cardiovascular	Individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD, as well as medical treatment with ACE inhibitors and/or beta-blockers); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy	Cardiovascular; Musculoskeletal; Neurologic	571956; 3275904; 9270668; 10958653; 12428213; 15111675; 16380616; 20301672; 21336781; 21676617

ClinVar

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

• not provided (2 variants)
• Myofibrillar myopathy 3 (2 variants)
• Myofibrillar myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYOT 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			4	65	1	70
missense	2	3	180	9		194
nonsense		1	5			6
start loss			1			1
frameshift			9	1		10
inframe indel			4			4
splice donor/acceptor (+/-2bp)			2			2
splice region			8	7	1	16
non coding			10	36	20	66
Total	2	4	215	111	21

Variants in MYOT

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

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

Position	Type	Phenotype	Significance	ClinVar
5-137867879-C-G		Myofibrillar myopathy 3	Uncertain significance (Feb 02, 2018)
5-137867914-A-G		Myofibrillar myopathy 3 • Limb-Girdle Muscular Dystrophy, Dominant	Benign/Likely benign (May 29, 2020)
5-137867932-C-A		Limb-Girdle Muscular Dystrophy, Dominant • Myofibrillar Myopathy, Dominant • Myofibrillar myopathy 3	Benign/Likely benign (Jan 13, 2018)
5-137870126-TA-T			Benign (Aug 10, 2019)
5-137870126-T-TA			Likely benign (Jan 28, 2020)
5-137870141-A-G			Benign (Oct 26, 2019)
5-137870267-T-A			Benign (Jul 15, 2018)
5-137870288-GACACAC-G			Benign (Nov 07, 2019)
5-137870288-G-GAC			Benign (Aug 06, 2019)
5-137870288-G-GACAC			Benign (Aug 06, 2019)
5-137870288-G-GACACAC			Benign (Aug 18, 2019)
5-137870288-G-GACACACAC			Benign (Aug 10, 2019)
5-137870288-G-GACACACACAC			Likely benign (Dec 07, 2019)
5-137870487-C-T		Myofibrillar Myopathy, Dominant • Limb-Girdle Muscular Dystrophy, Dominant • Myofibrillar myopathy 3	Uncertain significance (Jun 14, 2016)
5-137870561-AG-A		Limb-Girdle Muscular Dystrophy, Dominant • Myofibrillar Myopathy, Dominant • Myofibrillar myopathy 3	Uncertain significance (Jun 14, 2016)
5-137870652-A-T		Myofibrillar myopathy 3	Uncertain significance (Feb 01, 2018)
5-137870663-C-T		Myofibrillar myopathy 3	Likely benign (Sep 13, 2023)
5-137870664-G-A		Myofibrillar myopathy 3	Uncertain significance (Jun 25, 2023)
5-137870667-C-G		Myofibrillar myopathy 3	Uncertain significance (Nov 12, 2023)
5-137870667-C-T		Myofibrillar myopathy 3	Uncertain significance (Oct 13, 2023)
5-137870668-G-A		Myofibrillar myopathy 3	Conflicting classifications of pathogenicity (Nov 22, 2022)
5-137870683-T-C		Myofibrillar myopathy 3	Uncertain significance (Jul 03, 2023)
5-137870685-C-G			Uncertain significance (Aug 09, 2016)
5-137870699-A-C		Myofibrillar myopathy 3	Likely benign (Jul 06, 2022)
5-137870700-T-A		Myofibrillar myopathy 3	Uncertain significance (Feb 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYOT	protein_coding	protein_coding	ENST00000239926	9	20061

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.37e-8	0.932	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.553	241	266	0.905	0.0000138	3249
Missense in Polyphen		85	98.185	0.86571		1179
Synonymous	-0.958	104	92.3	1.13	0.00000447	959
Loss of Function	1.86	16	26.3	0.609	0.00000135	310

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000794	0.000793
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000186	0.000185
Middle Eastern	0.000163	0.000163
South Asian	0.000589	0.000588
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a complex of multiple actin cross-linking proteins. Involved in the control of myofibril assembly and stability at the Z lines in muscle cells. {ECO:0000269|PubMed:12499399}.
• Disease: DISEASE: Myopathy, myofibrillar, 3 (MFM3) [MIM:609200]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM3 is characterized by progressive skeletal muscle weakness greater distally than proximally, tight heel cords, hyporeflexia, cardiomyopathy and peripheral neuropathy in some patients. Affected muscle exhibits disorganization and streaming of the Z-line, presence of large hyaline structures, excessive accumulation of myotilin and other ectopically expressed proteins and prominent congophilic deposits. {ECO:0000269|PubMed:15111675}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spheroid body myopathy (SBM) [MIM:182920]: Autosomal dominant form of myofibrillar myopathy (MFM), characterized by slowly progressing proximal muscle weakness and dysarthric nasal speech. There is no evidence of cardiomyopathy. Muscle biopsy shows spheroid bodies within the type I muscle fibers. {ECO:0000269|PubMed:16380616}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.227

Intolerance Scores

• loftool: 0.923
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.06

Haploinsufficiency Scores

• pHI: 0.606
• hipred: N
• hipred_score: 0.486
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.135

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myot
• Phenotype: normal phenotype

Zebrafish Information Network

• Gene name: myot
• Affected structure: skeletal muscle
• Phenotype tag: abnormal
• Phenotype quality: refractivity

Gene ontology

• Biological process: muscle contraction;homophilic cell adhesion via plasma membrane adhesion molecules;axon guidance;synapse organization
• Cellular component: plasma membrane;actin cytoskeleton;Z disc;axon;sarcolemma;neuronal cell body
• Molecular function: actin binding;protein binding;axon guidance receptor activity;structural constituent of muscle;alpha-actinin binding