Sick sinus syndrome 2, autosomal dominant: genes and variants

Genes linked to Sick sinus syndrome 2, autosomal dominant

• HCN4: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

  Its hyperpolarization-activated current contributes substantially to spontaneous diastolic depolarization in sinoatrial-node pacemaker cells. Pathogenic variants can cause sinus bradycardia, conduction abnormalities, and in some families left-ventricular noncompaction.

  4 disease-causing and 76 uncertain variants in HCN4 are linked to Sick sinus syndrome 2, autosomal dominant.

• 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.

  2 disease-causing and 58 uncertain variants in SCN5A are linked to Sick sinus syndrome 2, autosomal dominant.

• 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.

  0 disease-causing and 62 uncertain variants in MYH6 are linked to Sick sinus syndrome 2, autosomal dominant.

Known disease-causing variants in Sick sinus syndrome 2, autosomal dominant

Same protein, different disease

• Brugada syndrome is also caused by HCN4 variants; they fall partly in the same places as the Sick sinus syndrome 2, autosomal dominant variants (9 disease-causing).
• Brugada syndrome is also caused by SCN5A variants; they fall mostly in different places as the Sick sinus syndrome 2, autosomal dominant variants (24 disease-causing).
• Cardiac arrhythmia is also caused by SCN5A variants; they fall mostly in different places as the Sick sinus syndrome 2, autosomal dominant variants (17 disease-causing).
• Long QT syndrome is also caused by SCN5A variants; they fall mostly in different places as the Sick sinus syndrome 2, autosomal dominant variants (16 disease-causing).
• Dilated cardiomyopathy is also caused by SCN5A variants; they fall mostly in different places as the Sick sinus syndrome 2, autosomal dominant variants (4 disease-causing).
• Progressive familial heart block is also caused by SCN5A variants; they fall mostly in different places as the Sick sinus syndrome 2, autosomal dominant variants (4 disease-causing).

Diseases related to Sick sinus syndrome 2, autosomal dominant

• Cardiac arrhythmia, also linked to HCN4 and SCN5A
• Primary dilated cardiomyopathy, also linked to MYH6 and SCN5A
• Brugada syndrome, also linked to HCN4 and SCN5A
• Long QT syndrome, also linked to SCN5A
• Hypertrophic cardiomyopathy, also linked to MYH6
• Dilated cardiomyopathy, also linked to SCN5A
• Epilepsy, idiopathic generalized, susceptibility to, 13, also linked to HCN4
• Atrial septal defect, also linked to MYH6
• Epilepsy, also linked to SCN5A
• Atrial fibrillation, familial, 10, also linked to SCN5A
• Primary familial hypertrophic cardiomyopathy, also linked to MYH6
• Primary familial dilated cardiomyopathy, also linked to MYH6

Frequently asked questions

Which genes are linked to Sick sinus syndrome 2, autosomal dominant?

In CATVariant, Sick sinus syndrome 2, autosomal dominant is linked to 3 analyzed proteins: HCN4 (Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4), SCN5A (Sodium channel protein type 5 subunit alpha) and MYH6 (Myosin-6).

How many genetic variants are linked to Sick sinus syndrome 2, autosomal dominant?

214 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 196 are of uncertain significance or have conflicting reports.

Which uncertain variants in Sick sinus syndrome 2, autosomal dominant 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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