Evidence map›Paper›PMID 42163949›Full record

ArticleHealth science reports2026

Genotype-Phenotype Discordance in Cardiomyopathies: Pathophysiology, Clinical Expression, and Therapeutic Considerations.

Abubakar Nazir, Atif Hussain Sarwar, Rameen Nazar, Sarim Hassan Shahab, Sumera Manan, Hafsa Rafique, Ahsan Talal Khan, Abdalhakim Shubietah, Syed Rafay Hussain Zaidi, Behram Khan

Abstract read
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Article in Health science reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Abubakar NazirDepartment of Internal Medicine The Jewish Hospital-Mercy Health Ohio USA.ORCID https://orcid.org/0000-0002-6650-6982
Atif Hussain SarwarDepartment of Internal Medicine Duke University Durham North Carolina USA.
Rameen NazarDepartment of Internal Medicine Bahria University of Health Sciences Campus Karachi Pakistan.
Sarim Hassan ShahabDepartment of Internal Medicine Nishtar Medical University Multan Pakistan.
Sumera MananDepartment of Internal Medicine Chandka Medical College Larkana Karachi Pakistan.
Hafsa RafiqueDepartment of Internal Medicine FMH College of Medicine and Dentistry Lahore Pakistan.
Ahsan Talal KhanDepartment of Internal Medicine Khyber Medical College Peshawar Pakistan.
Abdalhakim ShubietahDepartment of Internal Medicine Advocate Illinois Masonic Medical Center Chicago Illinois USA.ORCID https://orcid.org/0000-0002-8300-0262
Syed Rafay Hussain ZaidiDepartment of Internal Medicine UC Health Parkview Medical Center Colorado USA.
Behram KhanDepartment of Internal Medicine Rochester Regional Health Rochester New York USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Cardiomyopathies encompass a spectrum of myocardial disorders often attributed to underlying genetic mutations. However, genotype-phenotype discordance where the genetic profile does not align with the expected clinical presentation poses significant diagnostic, prognostic, and therapeutic challenges. Objective: To review the mechanisms underlying genotype-phenotype discordance in cardiomyopathies, explore its clinical implications, and propose future research directions to bridge the gap between molecular findings and patient outcomes. Methods: A narrative review was conducted using PubMed, Scopus, and Embase for articles published between 2000 and 2025. Search terms included "genotype-phenotype discordance", "cardiomyopathy", "penetrance", "expressivity", "modifier genes", and "epigenetics". Included studies focused on genetic and clinical variability in hypertrophic, dilated, arrhythmogenic, and restrictive cardiomyopathies. Priority was given to cohort studies, family-based analyses, and mechanistic investigations addressing epigenetic, polygenic, and environmental contributors to phenotypic heterogeneity. Results: Multiple factors contribute to genotype-phenotype discordance in cardiomyopathies, including incomplete penetrance, variable expressivity, epigenetic regulation, modifier genes, and environmental influences such as exercise and comorbidities. This discordance complicates risk stratification and personalized therapy. Clinically, individuals with pathogenic variants may remain asymptomatic, while others without identified mutations may exhibit overt disease. Emerging tools such as polygenic risk scores, multi-omics integration, and longitudinal phenotyping are improving phenotype prediction. Conclusion: Genotype-phenotype discordance in cardiomyopathies underscores the complexity of translating genetic insights into clinical practice. A multidimensional approach combining genetic, molecular, and environmental data is essential to refine diagnosis, guide management, and inform genetic counseling. Future research should focus on deep phenotyping, systems biology, and longitudinal cohort studies to unravel the dynamic interplay between genes and environment.

Indexed as

cardiomyopathyepigeneticsexpressivitygenetic variabilitygenotype–phenotype correlationpenetranceprecision medicine

Identifiers

PMID42163949
PMCPMC13183774

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.