Familial cardiomyopathy: genes and variants

Genes linked to Familial 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.

  7 disease-causing and 0 uncertain variants in MYH7 are linked to Familial 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.

  1 disease-causing and 1 uncertain variants in TPM1 are linked to Familial 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.

  0 disease-causing and 0 uncertain variants in LMNA are linked to Familial cardiomyopathy.

Where Familial cardiomyopathy variants cluster

• MYH7 Myosin motor (positions 85–778): 7 of 7 disease-causing changes, 2.8× more than its size predicts.

Known disease-causing variants in Familial cardiomyopathy

Which prediction tools work for Familial cardiomyopathy

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

• CATVariant: 86 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 80 out of 100
• PolyPhen-2: 64 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Same protein, different disease

• Hypertrophic cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Familial cardiomyopathy variants (239 disease-causing).
• Dilated cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Familial cardiomyopathy variants (21 disease-causing).
• Primary dilated cardiomyopathy is also caused by MYH7 variants; they fall mostly in different places as the Familial cardiomyopathy variants (15 disease-causing).
• Myosin storage myopathy is also caused by MYH7 variants; they fall mostly in different places as the Familial cardiomyopathy variants (13 disease-causing).
• MYH7-related skeletal myopathy is also caused by MYH7 variants; they fall mostly in different places as the Familial cardiomyopathy variants (7 disease-causing).
• Hypertrophic cardiomyopathy is also caused by TPM1 variants; they fall mostly in different places as the Familial cardiomyopathy variants (15 disease-causing).
• Primary dilated cardiomyopathy is also caused by TPM1 variants; they fall mostly in different places as the Familial cardiomyopathy variants (6 disease-causing).
• Dilated cardiomyopathy is also caused by TPM1 variants; they fall mostly in different places as the Familial cardiomyopathy variants (6 disease-causing).

Diseases related to Familial cardiomyopathy

• Dilated cardiomyopathy, also linked to LMNA, MYH7 and TPM1
• Primary dilated cardiomyopathy, also linked to LMNA, MYH7 and TPM1
• Hypertrophic cardiomyopathy, also linked to MYH7 and TPM1
• Left ventricular noncompaction, also linked to MYH7 and TPM1
• Primary familial dilated cardiomyopathy, also linked to LMNA and MYH7
• Familial isolated dilated cardiomyopathy, also linked to MYH7 and TPM1
• Charcot-Marie-Tooth disease, also linked to LMNA
• Bethlem myopathy, also linked to LMNA
• Atrial septal defect, also linked to TPM1
• Arrhythmogenic right ventricular dysplasia, also linked to LMNA
• Primary familial hypertrophic cardiomyopathy, also linked to MYH7
• Myosin storage myopathy, also linked to MYH7

Frequently asked questions

Which genes are linked to Familial cardiomyopathy?

In CATVariant, Familial cardiomyopathy is linked to 3 analyzed proteins: MYH7 (Myosin-7), TPM1 (Tropomyosin alpha-1 chain) and LMNA (Prelamin-A/C).

How many genetic variants are linked to Familial cardiomyopathy?

10 variants: 8 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 1 are of uncertain significance or have conflicting reports.

Which uncertain variants in Familial cardiomyopathy look disease-causing?

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

Which variant effect predictor works best for Familial cardiomyopathy?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.80, based on 8 disease-causing and 23 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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