MYOZ2

myozenin 2, the group of Myozenins

Basic information

Region (hg38): 4:119135832-119187789

Previous symbols: [ "C4orf5" ]

Links

ENSG00000172399 ∙ NCBI:51778 ∙ OMIM:605602 ∙ HGNC:1330 ∙ Uniprot:Q9NPC6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 16 (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy 16 (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy 16 (Limited), mode of inheritance: AD
• hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic, 16	AD	Cardiovascular	Surveillance and preventive measures related to cardiac manifestations, which have been reported as including arrhythmias, may allow early diagnosis and medical management as well as pacemaker placement, which may reduce morbidity and mortality	Cardiovascular	17347475; 19472918

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYOZ2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYOZ2 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			1	31	4	36
missense		1	115	3		119
nonsense			5			5
start loss			1			1
frameshift			5			5
inframe indel						0
splice donor/acceptor (+/-2bp)			3			3
splice region			3	4		7
non coding			6	17	21	44
Total	0	1	136	51	25

Variants in MYOZ2

This is a list of pathogenic ClinVar variants found in the MYOZ2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-119135910-A-G			Likely benign (Apr 08, 2019)
4-119135955-C-T		not specified	Benign (Apr 30, 2014)
4-119135956-G-A		not specified	Likely benign (Jun 26, 2017)
4-119135991-G-GT		Hypertrophic cardiomyopathy • Hypertrophic cardiomyopathy 16	Benign/Likely benign (Aug 27, 2021)
4-119136010-C-T			Benign (Jun 23, 2018)
4-119136254-C-A			Likely benign (May 19, 2020)
4-119136400-G-A			Benign (Jun 19, 2018)
4-119136492-T-C		not specified	Likely benign (Mar 10, 2017)
4-119136516-C-CA		not specified • Hypertrophic cardiomyopathy 16 • Cardiovascular phenotype • Cardiomyopathy	Benign (Feb 13, 2018)
4-119136523-A-G		not specified • Cardiovascular phenotype	Uncertain significance (Apr 14, 2016)
4-119136526-A-T		Hypertrophic cardiomyopathy • Hypertrophic cardiomyopathy 16 • Cardiovascular phenotype	Uncertain significance (Jul 17, 2023)
4-119136536-A-T		Hypertrophic cardiomyopathy • Hypertrophic cardiomyopathy 16 • Cardiovascular phenotype	Uncertain significance (Aug 28, 2023)
4-119136542-C-G		not specified • Hypertrophic cardiomyopathy • Cardiomyopathy • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Oct 13, 2023)
4-119136544-A-G		Hypertrophic cardiomyopathy • Cardiovascular phenotype • Hypertrophic cardiomyopathy 16	Uncertain significance (Dec 26, 2023)
4-119136545-T-C		Cardiovascular phenotype	Uncertain significance (Dec 29, 2020)
4-119136552-G-C		Hypertrophic cardiomyopathy	Uncertain significance (Apr 30, 2022)
4-119136554-A-C		not specified • Cardiovascular phenotype • Hypertrophic cardiomyopathy • Hypertrophic cardiomyopathy 16 • Hypertrophic cardiomyopathy;Cardiomyopathy • Cardiomyopathy	Benign/Likely benign (Jan 18, 2024)
4-119136554-A-G		not specified • Cardiovascular phenotype • Hypertrophic cardiomyopathy • Cardiomyopathy • Hypertrophic cardiomyopathy 16	Uncertain significance (Mar 14, 2022)
4-119136561-A-C		Hypertrophic cardiomyopathy	Uncertain significance (Oct 08, 2021)
4-119136564-G-A		not specified • Hypertrophic cardiomyopathy 16 • Cardiovascular phenotype • Hypertrophic cardiomyopathy	Benign/Likely benign (Jun 22, 2020)
4-119136572-C-T		Hypertrophic cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Nov 21, 2023)
4-119136579-C-CA		Hypertrophic cardiomyopathy	Uncertain significance (Aug 03, 2022)
4-119136582-G-A		Cardiovascular phenotype	Uncertain significance (Dec 19, 2018)
4-119136600-T-C		Cardiovascular phenotype • Hypertrophic cardiomyopathy • not specified	Conflicting classifications of pathogenicity (Apr 26, 2023)
4-119136609-T-C		Hypertrophic cardiomyopathy • not specified	Conflicting classifications of pathogenicity (Jul 29, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYOZ2	protein_coding	protein_coding	ENST00000307128	5	52006

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00157	0.893	125721	0	24	125745	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.539	125	143	0.873	0.00000693	1746
Missense in Polyphen		44	53.059	0.82927		647
Synonymous	-0.0712	49	48.4	1.01	0.00000225	498
Loss of Function	1.41	6	11.1	0.543	5.63e-7	138

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000214	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000326	0.000326
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Myozenins may serve as intracellular binding proteins involved in linking Z line proteins such as alpha-actinin, gamma- filamin, TCAP/telethonin, LDB3/ZASP and localizing calcineurin signaling to the sarcomere. Plays an important role in the modulation of calcineurin signaling. May play a role in myofibrillogenesis.

Recessive Scores

• pRec: 0.158

Intolerance Scores

• loftool: 0.568
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.508
• hipred: Y
• hipred_score: 0.615
• ghis: 0.525

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.323

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myoz2
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;skeletal muscle tissue development;biological_process;skeletal muscle fiber adaptation;sarcomere organization;negative regulation of calcineurin-NFAT signaling cascade
• Cellular component: actin cytoskeleton;sarcomere;Z disc
• Molecular function: actin binding;protein binding;protein phosphatase 2B binding;telethonin binding;FATZ binding