Primary familial dilated cardiomyopathy: genes and variants

Genes linked to Primary familial 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.

  3 disease-causing and 5 uncertain variants in LMNA are linked to Primary familial 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.

  2 disease-causing and 3 uncertain variants in RBM20 are linked to Primary familial dilated cardiomyopathy.

• MYH6: Myosin-6

  Its alpha-myosin motor contributes to ATP-dependent force generation in the cardiac sarcomere, particularly in atrial myocardium. Pathogenic variants can cause cardiomyopathy, congenital heart defects, and selected conduction-system disorders.

  1 disease-causing and 2 uncertain variants in MYH6 are linked to Primary familial 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.

  1 disease-causing and 2 uncertain variants in TNNT2 are linked to Primary familial 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.

  1 disease-causing and 1 uncertain variants in DES are linked to Primary familial 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.

  1 disease-causing and 0 uncertain variants in MYH7 are linked to Primary familial 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.

  0 disease-causing and 5 uncertain variants in LDB3 are linked to Primary familial dilated cardiomyopathy.

Weakly linked (only a few uncertain records): ABCC9, BAG3, KCNH2, MYPN, SCN5A, VCL, DSC2, DSP and 2 more.

Known disease-causing variants in Primary familial dilated cardiomyopathy

Which prediction tools work for Primary familial dilated cardiomyopathy

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

• CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 85 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Charcot-Marie-Tooth disease is also caused by LMNA variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (130 disease-causing).
• Dilated cardiomyopathy is also caused by LMNA variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (21 disease-causing).
• Familial partial lipodystrophy, Dunnigan type is also caused by LMNA variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (13 disease-causing).
• Emery-Dreifuss muscular dystrophy is also caused by LMNA variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (12 disease-causing).
• Congenital muscular dystrophy due to LMNA mutation is also caused by LMNA variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (11 disease-causing).
• Dilated cardiomyopathy 1DD is also caused by RBM20 variants; they fall partly in the same places as the Primary familial dilated cardiomyopathy variants (4 disease-causing).
• Hypertrophic cardiomyopathy is also caused by TNNT2 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (20 disease-causing).
• Dilated cardiomyopathy is also caused by TNNT2 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (18 disease-causing).
• Cardiomyopathy, familial restrictive, 3 is also caused by TNNT2 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (16 disease-causing).
• Primary dilated cardiomyopathy is also caused by TNNT2 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (7 disease-causing).
• Familial isolated dilated cardiomyopathy is also caused by TNNT2 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (3 disease-causing).
• Desmin-related myofibrillar myopathy is also caused by DES variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (37 disease-causing).
• Dilated cardiomyopathy is also caused by DES variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (5 disease-causing).
• Primary dilated cardiomyopathy is also caused by DES variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (3 disease-causing).
• Neurogenic scapuloperoneal syndrome, Kaeser type is also caused by DES variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (3 disease-causing).
• Hypertrophic cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (239 disease-causing).
• Dilated cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (21 disease-causing).
• Primary dilated cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (15 disease-causing).
• Myosin storage myopathy is also caused by MYH7 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (13 disease-causing).
• MYH7-related skeletal myopathy is also caused by MYH7 variants; they fall mostly in different places as the Primary familial dilated cardiomyopathy variants (7 disease-causing).

Diseases related to Primary familial dilated cardiomyopathy

• Dilated cardiomyopathy, also linked to DES, LDB3, LMNA, MYH7 and 2 more
• Primary dilated cardiomyopathy, also linked to DES, LMNA, MYH6, MYH7 and 2 more
• Familial isolated dilated cardiomyopathy, also linked to DES, MYH6, MYH7, RBM20 and 1 more
• Hypertrophic cardiomyopathy, also linked to LDB3, MYH6, MYH7 and TNNT2
• Left ventricular noncompaction, also linked to LDB3, MYH7 and TNNT2
• Primary familial hypertrophic cardiomyopathy, also linked to MYH6 and MYH7
• Myofibrillar myopathy, also linked to DES and LDB3
• Familial cardiomyopathy, also linked to LMNA and MYH7
• Arrhythmogenic right ventricular cardiomyopathy, also linked to DES and MYH7
• Limb-girdle muscular dystrophy, also linked to DES and LMNA
• Charcot-Marie-Tooth disease, also linked to LMNA
• Bethlem myopathy, also linked to LMNA

Frequently asked questions

Which genes are linked to Primary familial dilated cardiomyopathy?

In CATVariant, Primary familial dilated cardiomyopathy is linked to 7 analyzed proteins: LMNA (Prelamin-A/C), RBM20 (RNA-binding protein 20), MYH6 (Myosin-6), TNNT2 (Troponin T, cardiac muscle), DES (Desmin), MYH7 (Myosin-7) and 1 more.

How many genetic variants are linked to Primary familial dilated cardiomyopathy?

43 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 34 are of uncertain significance or have conflicting reports.

Which uncertain variants in Primary familial dilated cardiomyopathy look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

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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