Related Experiment Video

Updated: Jan 13, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
07:15

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation

Published on: January 16, 2019

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Cardiovascular prognostic impact of missense vs nonmissense lamin A/C variants: A systematic review and meta-analysis

Andrea Igoren Guaricci1, Andrea Faggiano2, Karim Wahbi3

  • 1University Cardiology Unit, Interdisciplinary Department of Medicine, University of Bari "Aldo Moro," Bari, Italy.

Heart Rhythm
|January 7, 2026
PubMed

Insights

Non-missense LMNA gene variants significantly increase the risk of cardiovascular events and arrhythmias compared to missense variants. Heart failure events, however, showed similar incidence between variant types.

Area of Science:

  • Genetics
  • Cardiology
  • Molecular Biology

Background:

  • LMNA gene variants cause laminopathies, leading to severe cardiovascular issues like arrhythmias and heart failure.
  • The distinct prognostic impact of missense versus non-missense LMNA variants is not well understood.

Purpose of the Study:

  • To compare cardiovascular outcomes, specifically malignant ventricular arrhythmias (MVA) and heart failure (HF), between patients with missense and non-missense LMNA variants.
  • To analyze MVA and HF events separately to understand their differential impact.

Main Methods:

  • A systematic review and meta-analysis adhering to PRISMA guidelines.
  • Searched databases including PubMed, OVID-MEDLINE, and Cochrane Library.
  • Employed fixed or random effects models for meta-analyses based on data heterogeneity.

Main Results:

  • Included 12 studies with 1818 participants (969 missense, 849 non-missense variants).
  • Non-missense variants were linked to higher overall cardiovascular events (30.5% vs. 21.3%, OR: 2.22, p < 0.001).
  • Malignant ventricular arrhythmias were more frequent in non-missense variant carriers (25.5% vs. 18.9%, OR: 2.37, p < 0.001), while HF events showed no significant difference.

Conclusions:

  • Non-missense LMNA variants confer a worse prognosis regarding cardiovascular outcomes, especially arrhythmias.
  • Heart failure incidence appears similar between missense and non-missense LMNA variant carriers, suggesting distinct pathogenic mechanisms.
Abstract

Keywords:
LMNALamin A/CLaminopathiesMissenseNonmissensePrognosis

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