MYL1

protein-coding

myosin light chain 1, the group of Myosin light chains, class 1

Gene summary

Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in fast skeletal muscle. Two transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_079420.3

Inheritance

ClinVar variants

P:1U:25B:14

Top phenotype

Congenital myopathy 14

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr2:210,290,150-210,315,174

External References & Databases

Ensembl (ENSG00000168530)

Transcript & Mutation Effects

hg38 • Region Span ~25.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital myopathy with reduced type 2 muscle fibersMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0034109

Submitter: PanelApp Australia

congenital myopathy with reduced type 2 muscle fibersSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0034109

Submitter: Orphanet

congenital myopathy with reduced type 2 muscle fibersLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0034109

Submitter: Ambry Genetics

congenital myopathy with reduced type 2 muscle fibersLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0034109

Submitter: Labcorp Genetics (formerly Invitae)

congenital myopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019952

Submitter: ClinGen

*MYL1* was reported in relation to autosomal recessive congenital myopathy in 2018 (Ravenscroft et al., PMID: 30215711). At least 2 unique variants (splicing, missense) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 2 probands in 1 publication (PMID: 30215711). This gene-disease association is supported by a zebrafish model (PMID: 30215711). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease pair was originally approved by the ClinGen Congenital Myopathies Working Group on 4/13/20 (SOP Version 7). It was reevaluated on 02/21/2025. As a result of this reevaluation no new evidence was identified and the classification remained at Limited.

congenital myopathy with reduced type 2 muscle fibersMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0034109

Submitter: G2P

Clinical Genomic Database (CGD)

Congenital myopathy 14AR

Manifestation: Musculoskeletal

Intervention: General

Rationale: 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

Refs: 30215711

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MYL1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 24

not providedTotal: 8

MYL1-related disorderTotal: 8

Congenital myopathy with reduced type 2 muscle fibersTotal: 5

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_079420.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				5 clinvar		5
missense			24 clinvar	2 clinvar	1 clinvar	27
nonsense		1 clinvar				1
start loss				1 clinvar	2 clinvar	3
frameshift				1 clinvar	2 clinvar	3
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	25	9	5	40

Highest pathogenic variant AF is 0.000010533464

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_079420.3	RefSeq	NP_524144.1	6	MANE Select
ENST00000352451.4	Ensembl	ENSP00000307280.4	6	MANE Select
NM_079422.3	RefSeq	NP_524146.1	6	Standard
ENST00000341685.8	Ensembl	ENSP00000343321.4	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endothelin Pathways
Association Between Physico-Chemical Features and Toxicity Associated Pathways
Striated Muscle Contraction
Regulation of Actin Cytoskeleton
G13 Signaling Pathway

Biological Process

muscle contraction
muscle filament sliding
cardiac muscle contraction

Molecular Function

calcium ion binding
structural constituent of muscle

Cellular Component

cytosol
muscle myosin complex
myofibril
sarcomere

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000352451
Coding exons: 6
Length: 25041
Individuals with no LoFs: 125732
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 125748
p: 0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.523	95	110	0.860	0.00000572	1284
Missense (PolyPhen)		41	35.422	1.1575		429
Synonymous	-0.504	45	40.9	1.10	0.00000237	370
Loss of Function	0.791	7	9.65	0.725	4.72e-7	117

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.00031	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory light chain of myosin. Does not bind calcium.;

Intolerance Scores

LoFtool: 0.278
RVIS EVS: -0.05
RVIS percentile EVS: 50.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.307

Gene Damage Prediction

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