Table 1

Gene	Protein Product	Function	Role in RCM
TNNI3	Cardiac troponin I	Regulates actomyosin ATPase activity	Increases myofibrillar Ca²⁺ sensitivity, impairs relaxation
TNNT2	Cardiac troponin T	Anchors troponin complex to tropomyosin	Alters sarcomere tension, causes diastolic stiffness
MYH7	β-myosin heavy chain	Force generation during contraction	Affects contractile velocity, may lead to fibrosis
MYBPC3	Myosin-binding protein C	Regulates sarcomere structure	Reduces compliance and diastolic function
DES	Desmin	Cytoskeletal scaffolding	Structural disarray, Z-disk disruption
FLNC	Filamin C	Crosslinks actin, mechanosensing	Cytoskeletal instability, arrhythmogenic risk
LMNA	Lamin A/C	Nuclear structure, transcriptional control	Impaired nuclear-cytoskeletal signaling
RBM20	RNA-binding motif protein	Alternative splicing regulator	Alters titin splicing, affects compliance
TAZ	Tafazzin	Cardiolipin remodeling in mitochondria	Energy metabolism defects, overlap with BTHS

Table 1: Major Genes Associated with Primary RCM And Their Functions

Table 2

Gene	Variant	Type	Phenotype	Inheritance
TNNI3	c.616G>A (p.R205H)	Missense	Childhood-onset RCM	AD
MYH7	c.2168G>A (p.R723Q)	Missense	RCM with conduction abnormalities	AD
FLNC	c.7255delG (frameshift)	Truncating	Adult-onset RCM with arrhythmia	AD
DES	c.1360C>T (p.R454W)	Missense	RCM with skeletal muscle involvement	AD
LMNA	c.1907T>A (p.L636*)	Nonsense	RCM + conduction block + SCD	AD
TAZ	c.527A > G, p.H176R	Splice-site/missense	RCM + skeletal myopathy (Barth syndrome)	XLR

Table 2: Reported Variants and Associated Phenotypes in RCM

AD: Autosomal Dominant, XLR: X linked Recessive

Tables at a glance

Table 1

Table 2

Figures at a glance

Figure 1

FIGURE 1

Figure 1: Molecular pathways and cellular structures are affected in RCM

This schematic illustrates the key molecular components and cellular structures implicated in the pathogenesis of restrictive cardiomyopathy. The sarcomere is shown with contractile proteins including MYH7, MYBPC3, and troponins (TNNI3, TNNT2), reflecting impaired myocardial contraction. The Z-disc/cytoskeleton is represented by FLNC, DES, and ACTN2, proteins critical for structural integrity and mechanotransduction. The nucleus features LMNA and RBM20, linked to nuclear envelope stability and transcriptional regulation. Mitochondrial dysfunction is illustrated by TAZ and MT-TL1, associated with impaired energy metabolism. The fibrotic response is highlighted through the TGF-β signaling pathway, a central mediator of myocardial fibrosis. Arrows depict downstream pathological consequences including increased myocardial stiffness, fibrotic remodeling, arrhythmias, and the risk of sudden cardiac death.