What question did this study set out to answer?

To update the clinical validity assessment of reported gene-disease relationships for dilated cardiomyopathy using the Clinical Genome Resource framework.

September 10, 2026CirculationOpen Access

An Updated Evidence Assessment of the Genetic Causes of Dilated Cardiomyopathy

Q: What is the clinical evidence from this study?

Study design: Systematic Review. Population: Dilated Cardiomyopathy. Intervention: ClinGen clinical validity framework vs. 2019-2020 ClinGen evaluation. Primary outcome: Clinical validity classification of gene-disease relationships.

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Why the study?

Emerging evidence regarding the diverse genetic architecture of DCM necessitated reassessment of the clinical relevance of implicated disease genes.

Design

Expert panel gene curation reassessment using the Clinical Genome Resource framework

Key result

The updated ClinGen assessment classified 35 gene-disease relationships as having high evidence (Definitive, Strong, or Moderate) for causing dilated cardiomyopathy, an increase of 16 from the prior evaluation.

Authors

EJElizabeth Jordan PGPhoenix L. Grover PPP. Parker

Discussion

Member takes

Overview

May support expanded DCM genetic testing panels; extends prior ClinGen curation for clinical and research use.

Key Points

To update the clinical validity assessment of reported gene-disease relationships for dilated cardiomyopathy using the Clinical Genome Resource framework.
Applied the ClinGen semiquantitative clinical validity classification framework with disease-specific specifications to categorize genes based on published evidence strength.
Re-evaluated previously assessed genes from 2019-2020 and evaluated newly reported gene-disease-mode of inheritance (MOI) relationships between 2024 and 2025.
Evaluated 68 genes representing 72 unique gene-disease-MOI relationships (51 previously evaluated and 17 newly assessed genes).
Classified 35 curations as high evidence (16 Definitive, 10 Strong, 9 Moderate), marking an increase of 16 high-evidence curations from the previous evaluation.
Identified 9 newly assessed genes with high evidence (BAG5, FLII, LMOD2, MYLK3, MYZAP, NRAP, PPA2, PPP1R13L, RPL3L) and upgraded 4 re-evaluated genes from low to high evidence (PLEKHM2, PRDM16, TBX20, TNNI3K).

Study Design

Type

Systematic Review

Structured PICO

Population

An expert panel evaluation of 68 genes to assess the strength of evidence for their causal relationship with monogenic, non-syndromic dilated cardiomyopathy.

Outcome

Clinical validity classification of gene-disease-mode of inheritance relationships for DCM

The updated Clinical Genome Resource assessment identified 35 high-evidence genes for dilated cardiomyopathy, significantly expanding the known genetic architecture to inform clinical genetic testing.

Limitations

DCM gene curation will require ongoing reassessments due to the continuing expansion of high-quality research data.

Cite This Study

Jordan et al. (2026) conducted a systematic review in Dilated Cardiomyopathy. ClinGen clinical validity framework vs. 2019-2020 ClinGen evaluation was evaluated on Clinical validity classification of gene-disease relationships. The updated ClinGen assessment classified 35 gene-disease relationships as having high evidence (Definitive, Strong, or Moderate) for causing dilated cardiomyopathy, an increase of 16 from the prior evaluation.

synapsesocial.com/papers/6aa27a0b58559d80afc72bfd https://doi.org/10.1161/circulationaha.126.080302

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September 10, 2026CirculationOpen Access

An Updated Evidence Assessment of the Genetic Causes of Dilated Cardiomyopathy

View Full Paper

Ask AI

Bookmark

Why the study?

Emerging evidence regarding the diverse genetic architecture of DCM necessitated reassessment of the clinical relevance of implicated disease genes.

Design

Expert panel gene curation reassessment using the Clinical Genome Resource framework

Key result

Authors

EJElizabeth Jordan PGPhoenix L. Grover PPP. Parker

Discussion

Member takes

Overview

May support expanded DCM genetic testing panels; extends prior ClinGen curation for clinical and research use.

Key Points

To update the clinical validity assessment of reported gene-disease relationships for dilated cardiomyopathy using the Clinical Genome Resource framework.
Applied the ClinGen semiquantitative clinical validity classification framework with disease-specific specifications to categorize genes based on published evidence strength.
Re-evaluated previously assessed genes from 2019-2020 and evaluated newly reported gene-disease-mode of inheritance (MOI) relationships between 2024 and 2025.
Evaluated 68 genes representing 72 unique gene-disease-MOI relationships (51 previously evaluated and 17 newly assessed genes).
Classified 35 curations as high evidence (16 Definitive, 10 Strong, 9 Moderate), marking an increase of 16 high-evidence curations from the previous evaluation.
Identified 9 newly assessed genes with high evidence (BAG5, FLII, LMOD2, MYLK3, MYZAP, NRAP, PPA2, PPP1R13L, RPL3L) and upgraded 4 re-evaluated genes from low to high evidence (PLEKHM2, PRDM16, TBX20, TNNI3K).

Study Design

Type

Systematic Review

Structured PICO

Population

An expert panel evaluation of 68 genes to assess the strength of evidence for their causal relationship with monogenic, non-syndromic dilated cardiomyopathy.

Outcome

Clinical validity classification of gene-disease-mode of inheritance relationships for DCM

Limitations

DCM gene curation will require ongoing reassessments due to the continuing expansion of high-quality research data.

Cite This Study

synapsesocial.com/papers/6aa27a0b58559d80afc72bfd https://doi.org/10.1161/circulationaha.126.080302

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