Features include always present findings: Internally nucleated skeletal muscle fibers, Type 1 muscle fiber predominance, and Increased variability in muscle fiber diameter; and common findings: Enlarged heart (cardiomegaly) and Congestive heart failure. 20 total HPO annotations.

ACTN2 encodes actinin alpha 2 (894 aa). F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein Highest expression in Muscle Skeletal (1,297 TPM) and Heart Left Ventricle (586.9 TPM).

Myopathy, congenital, with structured cores and z-line abnormalities is associated with mutations in the ACTN2 gene on chromosome 1.

The ACTN2 protein participates in CaMKII and LRRC7 bind to NMDA receptors at postsynaptic density and Negative regulation of NMDA receptor-mediated neuronal transmission pathways.

ACTN2 is classified as a druggable target (Druggable Genome and Transporter categories) with score 4.7.

82 pathogenic variants reported in ACTN2 in ClinVar, including hotspot variants 1220240 and 986096.

Genetic testing for ACTN2 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for myopathy, congenital, with structured cores and z-line abnormalities has been reported in the published literature.

Phenotype severity distribution: 3 always present features, 2 common features.

No clinical trials have been registered for myopathy, congenital, with structured cores and z-line abnormalities.

117 publications have been identified in PubMed for myopathy, congenital, with structured cores and z-line abnormalities. Research spans Review / Meta-Analysis (50%), Basic Science / Preclinical (41%), and Diagnostic / Biomarker (3%).