MYL2

myosin light chain 2, the group of Myosin light chains, class 2

Basic information

Region (hg38): 12:110909996-111052434

Links

ENSG00000111245 ∙ NCBI:4633 ∙ OMIM:160781 ∙ HGNC:7583 ∙ Uniprot:P10916 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypertrophic cardiomyopathy 10 (Strong), mode of inheritance: AD
• congenital fiber-type disproportion myopathy (Supportive), mode of inheritance: AD
• hypertrophic cardiomyopathy 10 (Strong), mode of inheritance: AD
• myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy (Moderate), mode of inheritance: AR
• hypertrophic cardiomyopathy 10 (Definitive), mode of inheritance: AD
• hypertrophic cardiomyopathy 10 (Definitive), mode of inheritance: AD
• hypertrophic cardiomyopathy (Definitive), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD
• arrhythmogenic right ventricular cardiomyopathy (No Known Disease Relationship), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, familial hypertrophic, 10	AD	Cardiovascular	Medical/surgical (ICD) management may ameliorate/prevent severe sequelae	Cardiovascular; Musculoskeletal	8673105; 9535554; 12404107; 21896538; 23365102

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYL2 gene.

• Hypertrophic cardiomyopathy 10 (1 variants)
• Cardiomyopathy (1 variants)
• Primary familial hypertrophic cardiomyopathy (1 variants)
• not provided (1 variants)
• Hypertrophic cardiomyopathy (1 variants)
• Cardiovascular phenotype (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYL2 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	75	1	77
missense	1	8	194			203
nonsense		1	8			9
start loss						0
frameshift		2	19			21
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)			9			9
splice region			16	30	2	48
non coding			11	70	41	122
Total	1	12	245	145	42

Variants in MYL2

This is a list of pathogenic ClinVar variants found in the MYL2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-110910911-C-T		Hypertrophic cardiomyopathy 10	Uncertain significance (Jan 13, 2018)
12-110910950-G-A			Benign (Mar 03, 2015)
12-110910960-T-G			Benign (Mar 03, 2015)
12-110910975-G-T		Hypertrophic cardiomyopathy 10	Conflicting classifications of pathogenicity (Jan 12, 2018)
12-110910993-G-A		Hypertrophic cardiomyopathy 10 • Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy;Hypertrophic cardiomyopathy 10	Uncertain significance (Jul 23, 2021)
12-110911024-G-C			Benign (Mar 03, 2015)
12-110911048-G-A			Benign (Mar 03, 2015)
12-110911059-G-C			Benign (Mar 03, 2015)
12-110911067-G-A		Hypertrophic cardiomyopathy 10 • not specified	Conflicting classifications of pathogenicity (May 15, 2023)
12-110911068-A-G			Likely benign (Oct 15, 2018)
12-110911074-C-T		Cardiomyopathy • Hypertrophic cardiomyopathy	Uncertain significance (Apr 03, 2023)
12-110911077-C-T		Hypertrophic cardiomyopathy 10	Likely benign (Feb 25, 2021)
12-110911079-A-C		Hypertrophic cardiomyopathy 10	Uncertain significance (Mar 06, 2020)
12-110911079-A-G		Congenital myopathy with fiber type disproportion	Likely pathogenic (May 27, 2021)
12-110911081-T-A		Hypertrophic cardiomyopathy 10	Likely pathogenic (Jun 27, 2022)
12-110911081-T-G		Hypertrophic cardiomyopathy 10	Uncertain significance (Aug 14, 2019)
12-110911082-C-A			Likely pathogenic (Jul 29, 2015)
12-110911082-C-G		Hypertrophic cardiomyopathy 10	Uncertain significance (Mar 23, 2021)
12-110911082-C-T		Hypertrophic cardiomyopathy 10	Uncertain significance (Oct 10, 2020)
12-110911082-CCTT-C		Cardiovascular phenotype	Uncertain significance (Mar 24, 2022)
12-110911082-CCTTCT-C		Cardiomyopathy	Likely pathogenic (Oct 07, 2020)
12-110911085-T-C		Hypertrophic cardiomyopathy 10	Uncertain significance (Jun 03, 2022)
12-110911088-C-T		Hypertrophic cardiomyopathy 10 • Cardiovascular phenotype	Uncertain significance (Sep 28, 2022)
12-110911090-T-C		not specified • Hypertrophic cardiomyopathy 10	Conflicting classifications of pathogenicity (Apr 11, 2022)
12-110911090-T-G		Hypertrophic cardiomyopathy • Hypertrophic cardiomyopathy 10 • not specified	Conflicting classifications of pathogenicity (Dec 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYL2	protein_coding	protein_coding	ENST00000228841	7	9904

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.73e-8	0.0899	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.396	86	97.0	0.887	0.00000581	1123
Missense in Polyphen		27	29.855	0.90437		398
Synonymous	-0.797	44	37.8	1.16	0.00000294	281
Loss of Function	-0.315	11	9.93	1.11	5.17e-7	114

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000206	0.000206
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000249	0.000246
Middle Eastern	0.000218	0.000217
South Asian	0.000229	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Contractile protein that plays a role in heart development and function (By similarity). Following phosphorylation, plays a role in cross-bridge cycling kinetics and cardiac muscle contraction by increasing myosin lever arm stiffness and promoting myosin head diffusion; as a consequence of the increase in maximum contraction force and calcium sensitivity of contraction force. These events altogether slow down myosin kinetics and prolong duty cycle resulting in accumulated myosins being cooperatively recruited to actin binding sites to sustain thin filament activation as a means to fine-tune myofilament calcium sensitivity to force (By similarity). During cardiogenesis plays an early role in cardiac contractility by promoting cardiac myofibril assembly (By similarity). {ECO:0000250|UniProtKB:P08733, ECO:0000250|UniProtKB:P51667}.
• Disease: DISEASE: Cardiomyopathy, familial hypertrophic 10 (CMH10) [MIM:608758]: 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. Rarely, patients present a variant of familial hypertrophic cardiomyopathy, characterized by mid-left ventricular chamber thickening. {ECO:0000269|PubMed:11102452, ECO:0000269|PubMed:12404107, ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12818575, ECO:0000269|PubMed:8673105, ECO:0000269|PubMed:9535554}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Focal adhesion - Homo sapiens (human);Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Tight junction - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Cardiac Progenitor Differentiation;Myometrial Relaxation and Contraction Pathways;Focal Adhesion;Striated Muscle Contraction;VEGFA-VEGFR2 Signaling Pathway;ccr3 signaling in eosinophils;pkc-catalyzed phosphorylation of inhibitory phosphoprotein of myosin phosphatase;alk in cardiac myocytes;rho cell motility signaling pathway;nfat and hypertrophy of the heart ;rac1 cell motility signaling pathway;Striated Muscle Contraction;Muscle contraction;Stabilization and expansion of the E-cadherin adherens junction;PAR4-mediated thrombin signaling events;PAR1-mediated thrombin signaling events;CDC42 signaling events;N-cadherin signaling events;RhoA signaling pathway (Consensus)

Recessive Scores

• pRec: 0.273

Intolerance Scores

• loftool: 0.606
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.249
• hipred: Y
• hipred_score: 0.573
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.809

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Myl2
• Phenotype: pigmentation 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); hematopoietic system phenotype; normal phenotype; 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); liver/biliary system phenotype; respiratory system phenotype; embryo phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: myl2b
• Affected structure: heart
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• Biological process: regulation of the force of heart contraction;regulation of striated muscle contraction;heart development;post-embryonic development;muscle filament sliding;negative regulation of cell growth;muscle cell fate specification;muscle fiber development;cardiac myofibril assembly;ventricular cardiac muscle tissue morphogenesis;heart contraction;cardiac muscle contraction;positive regulation of the force of heart contraction
• Cellular component: cytosol;cytoskeleton;actin cytoskeleton;myosin complex;myofibril;sarcomere;A band;cardiac myofibril
• Molecular function: actin monomer binding;calcium ion binding;protein binding;structural constituent of muscle;myosin heavy chain binding