MYPN

myopalladin, the group of I-set domain containing

Basic information

Region (hg38): 10:68087896-68212017

Links

ENSG00000138347 ∙ NCBI:84665 ∙ OMIM:608517 ∙ HGNC:23246 ∙ Uniprot:Q86TC9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dilated cardiomyopathy 1KK (Limited), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• familial isolated restrictive cardiomyopathy (Supportive), mode of inheritance: AD
• childhood-onset nemaline myopathy (Supportive), mode of inheritance: AD
• cap myopathy (Supportive), mode of inheritance: AD
• dilated cardiomyopathy 1KK (Limited), mode of inheritance: AD
• MYPN-related myopathy (Strong), mode of inheritance: AR
• MYPN-related myopathy (Definitive), mode of inheritance: AR
• hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1KK; Cardiomyopathy, familial hypertrophic, 22; Cardiomyopathy, dilated, 1KK	AD	Cardiovascular	Surveillance (eg, including echocardiogram and electrocardiogram) and preventive measures related to cardiac manifestations may allow early diagnosis and management, which may reduce morbidity and mortality	Cardiovascular; Neurologic	18006477; 22286171; 22892539; 28017374

ClinVar

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

• Dilated cardiomyopathy 1KK (1000 variants)
• Cardiovascular phenotype (532 variants)
• not provided (452 variants)
• not specified (151 variants)
• Dilated cardiomyopathy 1KK;MYPN-related myopathy (58 variants)
• MYPN-related myopathy;Dilated cardiomyopathy 1KK (43 variants)
• Inborn genetic diseases (25 variants)
• MYPN-related myopathy (19 variants)
• Primary dilated cardiomyopathy (15 variants)
• MYPN-related condition (8 variants)
• Cardiomyopathy (7 variants)
• Primary familial hypertrophic cardiomyopathy (7 variants)
• Hypertrophic cardiomyopathy (5 variants)
• Primary familial dilated cardiomyopathy (4 variants)
• Dilated cardiomyopathy 1A (3 variants)
• See cases (2 variants)
• Familial hypertrophic cardiomyopathy 22 (2 variants)
• Left ventricular noncompaction cardiomyopathy (2 variants)
• Arrhythmogenic right ventricular cardiomyopathy (1 variants)
• Left ventricular noncompaction 1 (1 variants)
• Restrictive cardiomyopathy (1 variants)
• Long QT syndrome (1 variants)
• Sudden unexplained death (1 variants)
• Hypertrophic cardiomyopathy;Cardiomyopathy (1 variants)
• Left ventricular hypertrophy (1 variants)
• Cardiomyopathy;Heart failure;Primary dilated cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYPN 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	300	8	312
missense			712	20	5	737
nonsense	9	3	3			15
start loss			1			1
frameshift	12	4	6			22
inframe indel			6			6
splice donor/acceptor (+/-2bp)		9	3			12
splice region			18	22	1	41
non coding			8	115	120	243
Total	21	16	743	435	133

Highest pathogenic variant AF is 0.0000132

Variants in MYPN

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

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

Position	Type	Phenotype	Significance	ClinVar
10-68109676-G-A		not specified	Likely benign (Mar 12, 2018)
10-68109732-C-T		not specified • MYPN-related myopathy;Dilated cardiomyopathy 1KK	Benign (Feb 23, 2022)
10-68113992-T-C			Likely benign (Nov 15, 2021)
10-68114079-G-A			Benign (Nov 15, 2019)
10-68114130-G-C			Likely benign (Jun 25, 2020)
10-68114347-C-CT			Benign (Feb 03, 2020)
10-68114347-C-CTT			Likely benign (Nov 19, 2019)
10-68114451-C-A			Likely benign (Nov 15, 2019)
10-68121288-A-T			Benign (Jun 19, 2018)
10-68121325-C-T			Benign (Jun 19, 2018)
10-68121346-A-T			Benign (Jun 18, 2018)
10-68121394-C-T			Benign (Jun 14, 2018)
10-68121440-T-C			Uncertain significance (Nov 01, 2023)
10-68121451-A-C		Dilated cardiomyopathy 1KK	Uncertain significance (Dec 24, 2017)
10-68121455-T-C		Dilated cardiomyopathy 1KK • Cardiovascular phenotype	Uncertain significance (Apr 22, 2023)
10-68121459-A-C		Dilated cardiomyopathy 1KK	Uncertain significance (Jan 01, 2023)
10-68121460-G-A		Dilated cardiomyopathy 1KK	Uncertain significance (Jul 14, 2021)
10-68121460-G-C		Dilated cardiomyopathy 1KK	Uncertain significance (Nov 08, 2022)
10-68121461-C-T		Cardiovascular phenotype	Uncertain significance (Dec 23, 2020)
10-68121472-A-G		Dilated cardiomyopathy 1KK • Cardiovascular phenotype	Uncertain significance (Apr 05, 2021)
10-68121473-T-C		Primary familial hypertrophic cardiomyopathy • Dilated cardiomyopathy 1KK • Cardiovascular phenotype	Uncertain significance (Jul 27, 2023)
10-68121476-C-G		Dilated cardiomyopathy 1KK	Uncertain significance (Aug 15, 2022)
10-68121477-T-C		not specified	Likely benign (Jan 25, 2018)
10-68121480-G-A		Dilated cardiomyopathy 1KK	Likely benign (Jun 23, 2023)
10-68121485-T-C		Dilated cardiomyopathy 1KK • Cardiovascular phenotype	Uncertain significance (Mar 09, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYPN	protein_coding	protein_coding	ENST00000358913	19	105863

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000261	1.00	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.129	716	726	0.986	0.0000422	8620
Missense in Polyphen		261	284.24	0.91823		3471
Synonymous	-0.804	292	275	1.06	0.0000170	2669
Loss of Function	4.65	21	59.8	0.351	0.00000347	677

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000322	0.000322
Ashkenazi Jewish	0.00	0.00
East Asian	0.000489	0.000489
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000489	0.000489
South Asian	0.0000653	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the sarcomere that tethers together nebulin (skeletal muscle) and nebulette (cardiac muscle) to alpha-actinin, at the Z lines. {ECO:0000269|PubMed:11309420}.
• Disease: DISEASE: Cardiomyopathy, dilated 1KK (CMD1KK) [MIM:615248]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:18006477, ECO:0000269|PubMed:22286171, ECO:0000269|PubMed:22892539}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial hypertrophic 22 (CMH22) [MIM:615248]: A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death. {ECO:0000269|PubMed:22286171}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cardiomyopathy, familial restrictive 4 (RCM4) [MIM:615248]: A heart disorder characterized by impaired filling of the ventricles with reduced diastolic volume, in the presence of normal or near normal wall thickness and systolic function. {ECO:0000269|PubMed:22286171}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Integrin-mediated Cell Adhesion (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.578
• rvis_EVS: 0.81
• rvis_percentile_EVS: 87.76

Haploinsufficiency Scores

• pHI: 0.286
• hipred: Y
• hipred_score: 0.511
• ghis: 0.475

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.559

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mypn
• Phenotype: muscle 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); normal phenotype

Gene ontology

• Biological process: homophilic cell adhesion via plasma membrane adhesion molecules;axon guidance;sarcomere organization;dendrite self-avoidance
• Cellular component: nucleus;plasma membrane;Z disc;axon;I band
• Molecular function: actin binding;protein binding;cytoskeletal protein binding;SH3 domain binding;muscle alpha-actinin binding;cell-cell adhesion mediator activity