Restrictive cardiomyopathy: genes and variants

Genes linked to Restrictive 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 0 uncertain variants in TNNI3 are linked to Restrictive 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.

  3 disease-causing and 0 uncertain variants in FLNC are linked to Restrictive 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 Restrictive 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.

  0 disease-causing and 0 uncertain variants in TNNC1 are linked to Restrictive cardiomyopathy.

Weakly linked (only a few uncertain records): MYH6 and MYL3.

Known disease-causing variants in Restrictive cardiomyopathy

Same protein, different disease

• Hypertrophic cardiomyopathy is also caused by TNNI3 variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (24 disease-causing).
• Cardiomyopathy, familial restrictive, 3 is also caused by TNNI3 variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (9 disease-causing).
• Dilated cardiomyopathy 1FF is also caused by TNNI3 variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (7 disease-causing).
• Hypertrophic cardiomyopathy is also caused by FLNC variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (10 disease-causing).
• Distal myopathy with posterior leg and anterior hand involvement is also caused by FLNC variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (9 disease-causing).
• Myofibrillar myopathy is also caused by FLNC variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (7 disease-causing).
• Hypertrophic cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (239 disease-causing).
• Dilated cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (21 disease-causing).
• Primary dilated cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (15 disease-causing).
• Myosin storage myopathy is also caused by MYH7 variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (13 disease-causing).
• MYH7-related skeletal myopathy is also caused by MYH7 variants; they fall mostly in different places as the Restrictive cardiomyopathy variants (7 disease-causing).

Diseases related to Restrictive cardiomyopathy

• Hypertrophic cardiomyopathy, also linked to FLNC, MYH7, TNNC1 and TNNI3
• Dilated cardiomyopathy, also linked to FLNC, MYH7, TNNC1 and TNNI3
• Familial isolated dilated cardiomyopathy, also linked to MYH7, TNNC1 and TNNI3
• Primary dilated cardiomyopathy, also linked to MYH7 and TNNI3
• Cardiomyopathy, familial restrictive, 3, also linked to TNNC1 and TNNI3
• Primary familial hypertrophic cardiomyopathy, also linked to MYH7 and TNNI3
• Dilated cardiomyopathy 1FF, also linked to TNNC1 and TNNI3
• Myopathy, also linked to FLNC and MYH7
• Myofibrillar myopathy, also linked to FLNC
• Myosin storage myopathy, also linked to MYH7
• Left ventricular noncompaction, also linked to MYH7
• Primary familial dilated cardiomyopathy, also linked to MYH7

Frequently asked questions

Which genes are linked to Restrictive cardiomyopathy?

In CATVariant, Restrictive cardiomyopathy is linked to 4 analyzed proteins: TNNI3 (Troponin I, cardiac muscle), FLNC (Filamin-C), MYH7 (Myosin-7) and TNNC1 (Troponin C, slow skeletal and cardiac muscles).

How many genetic variants are linked to Restrictive cardiomyopathy?

16 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 2 are of uncertain significance or have conflicting reports.

Which uncertain variants in Restrictive 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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