The Multifaceted Role of the FLNC Gene in Hereditary Cardiomyopathies and Prognosis

Q: What is the clinical evidence from this study?

Study design: Review. Population: Hereditary cardiomyopathies associated with FLNC variants. Intervention: FLNC gene variants.

Q: What does this research mean for the field?

FLNC truncating variants predominantly cause dilated and arrhythmogenic cardiomyopathies via haploinsufficiency, whereas specific missense variants lead to hypertrophic or restrictive cardiomyopathies through protein aggregation. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Maria D’Apolito; Alessandra Ranaldi; Teresa Gaudiano; Angela Bruna Maffione; Rosa Santacroce; Giovanna D’Andrea; Massimo Iacoviello; Maurizio Margaglione

doi:10.3390/genes17091136

September 17, 2026GenesOpen Access

The Multifaceted Role of the FLNC Gene in Hereditary Cardiomyopathies and Prognosis

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Key result

FLNC truncating variants are predominantly associated with dilated and arrhythmogenic cardiomyopathies with high arrhythmic risk, whereas specific missense variants are linked to hypertrophic or restrictive cardiomyopathies.

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Key Points

To review the molecular biology, genotype-phenotype correlations, cardiac imaging features, and arrhythmic risks associated with FLNC gene variants in hereditary cardiomyopathies.
Conducted a narrative review searching PubMed/MEDLINE from inception to 17 July 2026 using terms combining 'FLNC' or 'filamin C' with various cardiomyopathy, arrhythmia, and valve prolapse terms.
Prioritized peer-reviewed human studies with genotype-phenotype correlations, imaging outcomes, and functional evidence, supplemented by clinical guidelines and biological mechanism studies without formal risk-of-bias scoring.
FLNC truncating variants cause haploinsufficiency via nonsense-mediated decay and strongly associate with dilated cardiomyopathy, nondilated left ventricular cardiomyopathy, and left-dominant arrhythmogenic cardiomyopathy accompanied by subepicardial or circumferential fibrosis and ventricular arrhythmias.
In a analyzed database snapshot of 3127 FLNC missense variants, 2968 (94.9%) were classified as variants of uncertain significance, whereas only 70 (2.2%) were pathogenic or likely pathogenic, correlating primarily with hypertrophic or restrictive cardiomyopathy through protein misfolding.
The average reported age of onset was 39.7 ± 14.5 years for FLNC-related dilated cardiomyopathy and 35.9 ± 14.8 years for hypertrophic cardiomyopathy.

Structured PICO

P

Population

Narrative review summarizing the role of FLNC gene variants in hereditary cardiomyopathies, including genotype-phenotype relationships and arrhythmic risk.

E

Exposure

FLNC gene variants (truncating and missense)

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Implication

Accurate classification of FLNC variants is essential for diagnosing specific cardiomyopathy phenotypes and guiding individualized prevention of sudden cardiac death.

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Cite This Study

D’Apolito et al. (2026) conducted a review in Hereditary cardiomyopathies associated with FLNC variants. FLNC gene variants was evaluated. FLNC truncating variants are predominantly associated with dilated and arrhythmogenic cardiomyopathies with high arrhythmic risk, whereas specific missense variants are linked to hypertrophic or restrictive cardiomyopathies.

synapsesocial.com/papers/6aad0b3bde0393d728b89775 https://doi.org/10.3390/genes17091136

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The Multifaceted Role of the FLNC Gene in Hereditary Cardiomyopathies and Prognosis

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Key Points

Structured PICO

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Implication

Abstract

Discussion

Cite This Study

The Multifaceted Role of the FLNC Gene in Hereditary Cardiomyopathies and Prognosis

Figures

Key Points

Structured PICO

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Implication

Abstract

Discussion

Cite This Study

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