Dilated cardiomyopathy: genes and variants

Genes linked to Dilated cardiomyopathy

• LMNA: Prelamin-A/C

  The gene product produces lamins A and C, structural proteins that form the nuclear lamina beneath the inner nuclear membrane. Lamins help maintain nuclear shape and organize chromatin, and LMNA variants are associated with muscular dystrophy, cardiomyopathy, lipodystrophy, and premature-aging syndromes.

  21 disease-causing and 69 uncertain variants in LMNA are linked to Dilated cardiomyopathy.

• MYH7: Myosin-7

  Its beta-myosin motor converts ATP hydrolysis into force within cardiac and slow-skeletal-muscle sarcomeres. Pathogenic variants are major causes of hypertrophic and dilated cardiomyopathy and can also produce inherited skeletal myopathies.

  21 disease-causing and 93 uncertain variants in MYH7 are linked to Dilated cardiomyopathy.

• TNNT2: Troponin T, cardiac muscle

  It anchors the cardiac troponin complex to tropomyosin and helps translate calcium-dependent conformational changes into controlled actin-myosin interaction. Pathogenic variants can cause hypertrophic, dilated, or restrictive cardiomyopathy and alter arrhythmic risk.

  18 disease-causing and 177 uncertain variants in TNNT2 are linked to Dilated cardiomyopathy.

• ACTC1: Actin, alpha cardiac muscle 1

  Its cardiac alpha-actin filaments form the core of the sarcomeric thin filament and provide the track against which myosin generates force. Pathogenic variants can cause hypertrophic or dilated cardiomyopathy and selected congenital heart defects.

  9 disease-causing and 190 uncertain variants in ACTC1 are linked to Dilated cardiomyopathy.

• TPM1: Tropomyosin alpha-1 chain

  It lies along actin filaments and helps control access of myosin to actin in response to troponin and calcium, while also stabilizing cytoskeletal actin in nonmuscle cells. Pathogenic variants can cause hypertrophic or dilated cardiomyopathy and several congenital myopathies.

  6 disease-causing and 18 uncertain variants in TPM1 are linked to Dilated cardiomyopathy.

• ABCC9: ATP-binding cassette sub-family C member 9

  A regulatory subunit of ATP-sensitive potassium (KATP) channels, partnering with KCNJ11 or KCNJ8 to control channel activation. It is a multi-pass membrane protein with important roles in cardiac and smooth-muscle excitability, and altered ABCC9 function is associated with cardiomyopathy, atrial fibrillation, and neurodevelopmental syndromes.

  5 disease-causing and 542 uncertain variants in ABCC9 are linked to Dilated cardiomyopathy.

• DES: Desmin

  Its desmin filaments mechanically integrate sarcomeres with the nucleus, mitochondria, and cell junctions in striated muscle. Pathogenic variants cause desmin-related myopathy and can produce cardiomyopathy, conduction disease, and skeletal-muscle weakness.

  5 disease-causing and 38 uncertain variants in DES are linked to Dilated cardiomyopathy.

• TNNC1: Troponin C, slow skeletal and cardiac muscles

  It binds calcium during each heartbeat and shifts the troponin complex to permit actin-myosin interaction and force generation in cardiac muscle. Pathogenic variants can alter calcium sensitivity and cause hypertrophic or dilated cardiomyopathy.

  4 disease-causing and 122 uncertain variants in TNNC1 are linked to Dilated cardiomyopathy.

• LDB3: LIM domain-binding protein 3

  It organizes Z-disc protein complexes and helps maintain sarcomere integrity during repeated muscle contraction. Pathogenic variants can cause myofibrillar myopathy and dilated or other forms of cardiomyopathy.

  4 disease-causing and 60 uncertain variants in LDB3 are linked to Dilated cardiomyopathy.

• SCN5A: Sodium channel protein type 5 subunit alpha

  Its rapid inward sodium current drives the upstroke of the cardiac action potential and enables fast electrical conduction through atrial, ventricular, and conduction-system tissue. Pathogenic variants can cause long-QT syndrome type 3, Brugada syndrome, conduction disease, and overlapping arrhythmia phenotypes.

  4 disease-causing and 17 uncertain variants in SCN5A are linked to Dilated cardiomyopathy.

• TNNI3: Troponin I, cardiac muscle

  It restrains cardiac actin-myosin interaction at low calcium and shifts position within the troponin complex when calcium binds, allowing contraction. Pathogenic variants can alter thin-filament calcium sensitivity and cause hypertrophic, restrictive, or dilated cardiomyopathy.

  3 disease-causing and 9 uncertain variants in TNNI3 are linked to Dilated cardiomyopathy.

• CSRP3: Cysteine and glycine-rich protein 3

  It localizes to the cardiac Z-disc and participates in mechanosensing and maintenance of sarcomere structure under mechanical load. Pathogenic variants can cause hypertrophic or dilated cardiomyopathy by disrupting cardiac structural signaling.

  2 disease-causing and 146 uncertain variants in CSRP3 are linked to Dilated cardiomyopathy.

• PLN: Phospholamban

  It tonically restrains SERCA2a-mediated calcium reuptake into the cardiac sarcoplasmic reticulum, with phosphorylation relieving this inhibition during adrenergic stimulation. Pathogenic variants can destabilize calcium cycling and cause dilated or arrhythmogenic cardiomyopathy.

  2 disease-causing and 35 uncertain variants in PLN are linked to Dilated cardiomyopathy.

• RBM20: RNA-binding protein 20

  It directs cardiac alternative splicing of TTN and numerous calcium-handling and sarcomeric transcripts. Pathogenic variants can produce a highly arrhythmogenic form of dilated cardiomyopathy through widespread disruption of cardiac RNA processing.

  1 disease-causing and 2 uncertain variants in RBM20 are linked to Dilated cardiomyopathy.

• PSEN1: Presenilin-1

  Its catalytic activity within gamma-secretase cleaves APP and many other membrane proteins, including Notch receptors. Pathogenic variants alter amyloid-beta production and are the most common known cause of autosomal dominant early-onset Alzheimer disease.

  1 disease-causing and 1 uncertain variants in PSEN1 are linked to Dilated cardiomyopathy.

• VCL: Vinculin

  It links integrins and cadherins to the actin cytoskeleton at focal adhesions and adherens junctions, transmitting mechanical force between cells and matrix. Pathogenic variants can cause dilated or hypertrophic cardiomyopathy and, in some cases, skeletal myopathy.

  0 disease-causing and 546 uncertain variants in VCL are linked to Dilated cardiomyopathy.

• TTN: Titin

  Its enormous titin polypeptide spans much of the sarcomere and provides passive elasticity, structural alignment, and mechanosensing in striated muscle. Truncating variants are among the most common genetic causes of dilated cardiomyopathy, while other variants cause diverse skeletal and cardiac myopathies.

  0 disease-causing and 4 uncertain variants in TTN are linked to Dilated cardiomyopathy.

• DMD: Dystrophin

  Its dystrophin product mechanically links the actin cytoskeleton of muscle fibers to the extracellular matrix and stabilizes the sarcolemma during contraction. Severe loss causes Duchenne muscular dystrophy, while variants preserving partial function more often cause Becker muscular dystrophy.

  0 disease-causing and 13 uncertain variants in DMD are linked to Dilated cardiomyopathy.

• TAFAZZIN: Tafazzin

  It remodels mitochondrial cardiolipin so the inner mitochondrial membrane can support efficient respiratory-chain organization and energy production. Loss-of-function variants cause Barth syndrome, characterized by cardiomyopathy, skeletal myopathy, neutropenia, growth delay, and abnormal cardiolipin composition.

  0 disease-causing and 1 uncertain variants in TAFAZZIN are linked to Dilated cardiomyopathy.

• BAG3: BAG family molecular chaperone regulator 3

  It coordinates chaperone-assisted protein quality control and autophagy, particularly in mechanically stressed cardiac and skeletal muscle. Pathogenic variants can impair sarcomere maintenance and cause dilated cardiomyopathy or myofibrillar myopathy.

  0 disease-causing and 0 uncertain variants in BAG3 are linked to Dilated cardiomyopathy.

• DSP: Desmoplakin

  It anchors intermediate filaments to desmosomes, allowing mechanically stressed tissues such as myocardium and epidermis to maintain strong cell-cell adhesion. Pathogenic variants can cause arrhythmogenic or dilated cardiomyopathy and a range of cardiocutaneous disorders.

  0 disease-causing and 1 uncertain variants in DSP are linked to Dilated cardiomyopathy.

• JPH2: Junctophilin-2

  It anchors the sarcoplasmic reticulum close to transverse tubules, creating junctional membrane domains required for tightly coupled calcium entry and calcium release in heart muscle. Pathogenic variants can disrupt excitation-contraction coupling and cause hypertrophic or dilated cardiomyopathy and inherited arrhythmia phenotypes.

  0 disease-causing and 0 uncertain variants in JPH2 are linked to Dilated cardiomyopathy.

• TBX20: T-box transcription factor TBX20

  It controls transcriptional programs required for cardiac chamber formation, septation, conduction-system development, and adult myocardial function. Heterozygous pathogenic variants can cause congenital heart defects and dilated cardiomyopathy.

  0 disease-causing and 0 uncertain variants in TBX20 are linked to Dilated cardiomyopathy.

• FLNC: Filamin-C

  It crosslinks actin and anchors signaling and structural proteins at Z-discs, costameres, and other mechanically stressed sites in striated muscle. Pathogenic variants can cause arrhythmogenic or dilated cardiomyopathy as well as myofibrillar and distal myopathies.

  0 disease-causing and 0 uncertain variants in FLNC are linked to Dilated cardiomyopathy.

• LAMP2: Lysosome-associated membrane glycoprotein 2

  It supports lysosomal membrane integrity, autophagic cargo delivery, and lysosome-mediated turnover, with particularly important roles in heart and skeletal muscle. Loss-of-function variants cause X-linked Danon disease, typically with hypertrophic cardiomyopathy, skeletal myopathy, and variable intellectual disability.

  0 disease-causing and 0 uncertain variants in LAMP2 are linked to Dilated cardiomyopathy.

• MYBPC3: Myosin-binding protein C, cardiac-type

  A cardiac thick-filament protein positioned in the cross-bridge region of striated muscle. It binds myosin and actin and helps tune contraction, while MYBPC3 variants are a leading genetic cause of hypertrophic cardiomyopathy.

  0 disease-causing and 0 uncertain variants in MYBPC3 are linked to Dilated cardiomyopathy.

• PSEN2: Presenilin-2

  Its gamma-secretase activity contributes to intramembrane cleavage of APP and other substrates in endolysosomal and cellular membranes. Pathogenic variants are a rare cause of autosomal dominant Alzheimer disease, generally with more variable penetrance and age of onset than PSEN1 variants.

  0 disease-causing and 17 uncertain variants in PSEN2 are linked to Dilated cardiomyopathy.

• ANKRD1: Ankyrin repeat domain-containing protein 1

  It localizes to the cardiac sarcomere and nucleus, where it participates in mechanosensing and stress-responsive transcription. Rare pathogenic variants have been associated with dilated and hypertrophic cardiomyopathy, although penetrance and variant-specific evidence can vary.

  0 disease-causing and 0 uncertain variants in ANKRD1 are linked to Dilated cardiomyopathy.

Weakly linked (only a few uncertain records): MYPN, ACTN2, CREBBP, GATA6, MYH6, MYL2, MYL3, NEDD4L and 2 more.

Where Dilated cardiomyopathy variants cluster

• MYH7 Myosin motor (positions 85–778): 17 of 21 disease-causing changes, 2.3× more than its size predicts.
• LMNA Coil 2 (positions 243–383): 11 of 21 disease-causing changes, 2.5× more than its size predicts.
• LMNA Head (positions 1–33): 3 of 21 disease-causing changes, 2.9× more than its size predicts.
• DES Coil 2B (positions 296–412): 3 of 5 disease-causing changes, 2.4× more than its size predicts.

Known disease-causing variants in Dilated cardiomyopathy

Showing 60 of 106.

Uncertain variants in Dilated cardiomyopathy that look disease-causing

Which prediction tools work for Dilated cardiomyopathy

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• MetaLR: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• REVEL: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• AlphaMissense: 88 out of 100
• SIFT: 83 out of 100
• CADD: 83 out of 100
• ESM1b (LLR): 82 out of 100
• PolyPhen-2: 82 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MutPred2: 78 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• EVE: 77 out of 100
• phyloP: 67 out of 100

Same protein, different disease

• Hypertrophic cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Dilated cardiomyopathy variants (239 disease-causing).
• Primary dilated cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Dilated cardiomyopathy variants (15 disease-causing).
• Myosin storage myopathy is also caused by MYH7 variants; they fall mostly in different places as the Dilated cardiomyopathy variants (13 disease-causing).
• MYH7-related skeletal myopathy is also caused by MYH7 variants; they fall mostly in different places as the Dilated cardiomyopathy variants (7 disease-causing).
• Familial cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Dilated cardiomyopathy variants (7 disease-causing).
• Charcot-Marie-Tooth disease is also caused by LMNA variants; they fall mostly in different places as the Dilated cardiomyopathy variants (130 disease-causing).
• Familial partial lipodystrophy, Dunnigan type is also caused by LMNA variants; they fall mostly in different places as the Dilated cardiomyopathy variants (13 disease-causing).
• Emery-Dreifuss muscular dystrophy is also caused by LMNA variants; they fall mostly in different places as the Dilated cardiomyopathy variants (12 disease-causing).
• Congenital muscular dystrophy due to LMNA mutation is also caused by LMNA variants; they fall partly in the same places as the Dilated cardiomyopathy variants (11 disease-causing).
• Hutchinson-Gilford syndrome is also caused by LMNA variants; they fall partly in the same places as the Dilated cardiomyopathy variants (9 disease-causing).
• Hypertrophic cardiomyopathy is also caused by TNNT2 variants; they fall in the same places as the Dilated cardiomyopathy variants (20 disease-causing).
• Primary dilated cardiomyopathy is also caused by TNNT2 variants; they fall mostly in different places as the Dilated cardiomyopathy variants (7 disease-causing).
• Familial isolated dilated cardiomyopathy is also caused by TNNT2 variants; they fall mostly in different places as the Dilated cardiomyopathy variants (3 disease-causing).
• Hypertrophic cardiomyopathy is also caused by TPM1 variants; they fall mostly in different places as the Dilated cardiomyopathy variants (15 disease-causing).
• Primary dilated cardiomyopathy is also caused by TPM1 variants; they fall mostly in different places as the Dilated cardiomyopathy variants (6 disease-causing).
• Desmin-related myofibrillar myopathy is also caused by DES variants; they fall mostly in different places as the Dilated cardiomyopathy variants (37 disease-causing).
• Primary dilated cardiomyopathy is also caused by DES variants; they fall mostly in different places as the Dilated cardiomyopathy variants (3 disease-causing).

Diseases related to Dilated cardiomyopathy

• Hypertrophic cardiomyopathy, also linked to ACTC1, BAG3, CSRP3, DSP and 13 more
• Familial isolated dilated cardiomyopathy, also linked to ABCC9, ACTC1, BAG3, CSRP3 and 12 more
• Primary dilated cardiomyopathy, also linked to ACTC1, ANKRD1, CSRP3, DES and 8 more
• Left ventricular noncompaction, also linked to ACTC1, LDB3, MYBPC3, MYH7 and 2 more
• Primary familial dilated cardiomyopathy, also linked to DES, LDB3, LMNA, MYH7 and 2 more
• Primary familial hypertrophic cardiomyopathy, also linked to JPH2, MYBPC3, MYH7 and TNNI3
• Myofibrillar myopathy, also linked to BAG3, DES, FLNC and LDB3
• Restrictive cardiomyopathy, also linked to FLNC, MYH7, TNNC1 and TNNI3
• Cardiac arrhythmia, also linked to DSP, SCN5A and TTN
• Atrial septal defect, also linked to ACTC1, TBX20 and TPM1
• Cardiomyopathy, familial restrictive, 3, also linked to TNNC1, TNNI3 and TNNT2
• Familial cardiomyopathy, also linked to LMNA, MYH7 and TPM1

Frequently asked questions

Which genes are linked to Dilated cardiomyopathy?

In CATVariant, Dilated cardiomyopathy is linked to 28 analyzed proteins: LMNA (Prelamin-A/C), MYH7 (Myosin-7), TNNT2 (Troponin T, cardiac muscle), ACTC1 (Actin, alpha cardiac muscle 1), TPM1 (Tropomyosin alpha-1 chain), ABCC9 (ATP-binding cassette sub-family C member 9) and 22 more.

How many genetic variants are linked to Dilated cardiomyopathy?

2,466 variants: 106 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2,106 are of uncertain significance or have conflicting reports.

Which uncertain variants in Dilated cardiomyopathy look disease-causing?

2 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example ACTC1 A333V and PLN R9H. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Dilated cardiomyopathy?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.88, based on 70 disease-causing and 234 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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