ClinGen Curation Activity Summary Report (2026-05-09)
Source Type, Affiliation, DOI
- Type: Database export — curated gene-disease validity, dosage sensitivity, and clinical actionability data
- Source: Clinical Genome Resource (ClinGen) Consortium — NIH-funded programme involving >100 expert gene curation expert panels (GCEPs)
- URL: https://clinicalgenome.org
- Data freshness: 2026-05-09 export
Overview
This report is the comprehensive ClinGen gene-disease curation database as of 2026-05-09, encompassing all curated gene-disease pairs with evidence classifications for: (1) gene-disease validity (definitive → strong → moderate → limited → disputed → refuting → no known disease relationship), (2) dosage sensitivity (haploinsufficiency and triplosensitivity scores), and (3) clinical actionability (actionability scores by adult and paediatric populations). The full file contains thousands of gene-disease pairs across all disease domains. For this cardiology wiki, 419 gene-disease curations spanning 258 unique cardiovascular genes were extracted as the primary reference material.
Keywords
Gene-disease validity, ClinGen, dosage sensitivity, haploinsufficiency, triplosensitivity, clinical actionability, GCEPs, variant classification, cardiovascular genetics
Key Takeaways
ClinGen Evidence Framework
- Definitive: >18 months of replication; overwhelming genetic and experimental evidence. Gene-disease relationship is established beyond reasonable doubt.
- Strong: Convincing genetic and experimental evidence; typically validated in multiple independent families/cohorts but <18 months or lacking some replication.
- Moderate: Emerging evidence; sufficient to warrant panel inclusion and clinical reporting, but some uncertainty remains.
- Limited: Some genetic or functional evidence, but insufficient for definitive causal claim; panel inclusion is debated.
- Disputed: Evidence refutes or fails to support previous gene-disease claim.
- Refuting: Multiple lines of evidence refute causation.
- No known disease relationship: Insufficient evidence to support association.
See concepts/ClinGen-Gene-Disease-Validity.
Hereditary Cardiovascular Disease — Summary Evidence Map (as of 2026-05-09)
Hypertrophic Cardiomyopathy (HCM)
| Gene |
Inheritance |
ClinGen Classification |
Date |
| MYBPC3 |
AD |
Definitive |
10/07/2021 |
| MYH7 |
AD |
Definitive |
07/12/2023 |
| TNNC1 |
AD |
Definitive |
09/13/2023 |
| TPM1 |
AD |
Definitive |
12/18/2023 |
| FHOD3 |
AD |
Definitive |
09/29/2023 |
| CSRP3 |
Semidominant |
Definitive |
08/09/2023 |
| ALPK3 |
AR |
Definitive |
02/09/2022 |
| ALPK3 |
AD |
Strong |
01/16/2025 |
| ACTC1 |
AD |
Definitive |
06/23/2021 |
| TNNI3 |
AD |
Definitive |
09/05/2017 |
| PLN |
AD |
Definitive (intrinsic CMP) |
02/12/2021 |
| LAMP2 |
X-linked |
Definitive (Danon) |
10/11/2017 |
| TTR |
AD |
Definitive (ATTR amyloidosis) |
12/11/2017 |
| CALR3 |
AD |
Disputing |
01/11/2023 |
| MYH6 |
AD |
Disputing |
07/12/2023 |
| CASQ2 |
AD |
Disputing |
05/10/2022 |
| DSP |
AD |
Disputing (HCM) |
06/22/2022 |
| VCL |
AD |
Disputing |
05/10/2023 |
| KCNQ1 |
AD |
Disputing |
05/09/2022 |
| ANKRD1 |
AD |
Disputing |
02/08/2023 |
| RYR2 |
AD |
Limited |
12/14/2022 |
| MYBPC3 |
AD/AR |
Limited (DCM) |
03/04/2026 / 05/16/2025 |
Dilated Cardiomyopathy (DCM)
| Gene |
Inheritance |
ClinGen Classification |
Date |
| TTN |
AD |
Definitive |
03/04/2026 |
| LMNA |
AD |
Definitive |
03/04/2026 |
| MYH7 |
AD |
Definitive |
03/04/2026 |
| SCN5A |
AD |
Definitive |
03/04/2026 |
| DES |
AD |
Definitive |
03/04/2026 |
| FLNC |
AD |
Definitive |
05/30/2025 |
| BAG3 |
AD |
Definitive |
03/04/2026 |
| RBM20 |
AD |
Definitive |
08/20/2020 |
| TNNC1 |
AD |
Definitive |
03/04/2026 |
| TNNT2 |
AD |
Definitive |
03/04/2026 |
| TNNI3 |
AD |
Strong |
03/04/2026 |
| TNNI3 |
AR |
Strong |
03/04/2026 |
| VCL |
AD |
Strong |
03/04/2026 |
| CSRP3 |
AD |
Limited |
03/04/2026 |
| TPM1 |
AD |
Moderate |
03/04/2026 |
| SGCD |
AD |
Limited |
03/04/2026 |
| DSG2 |
AD |
Limited |
03/04/2026 |
| CDH2 |
AD |
Limited |
05/16/2025 |
| CTF1 |
AD |
Limited |
02/20/2026 |
| BAG5 |
AR |
Moderate |
03/04/2026 |
| MYH6 |
AD |
Limited |
03/04/2026 |
| ANKRD1 |
AD |
Limited |
02/07/2025 |
| CAMK2D |
AD |
Strong |
10/15/2025 |
| PKP2 |
AD |
Disputing (DCM) |
05/30/2025 |
| RYR2 |
AD |
Limited |
01/10/2025 |
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
| Gene |
Inheritance |
ClinGen Classification |
Date |
| PKP2 |
AD |
Definitive |
03/08/2018 |
| DSG2 |
AD |
Definitive |
09/14/2018 |
| DSC2 |
AD |
Definitive |
09/14/2018 |
| TMEM43 |
AD |
Definitive |
10/26/2018 |
| DSP |
AD |
Definitive (ACM + wooly hair + keratoderma) |
05/30/2025 |
| PLN |
AD |
Moderate |
12/17/2020 |
| DES |
AD |
Moderate |
09/11/2018 |
| CDH2 |
AD |
Limited |
07/13/2018 |
| CTNNA3 |
AD |
Limited |
08/06/2019 |
| SCN5A |
AD |
Limited |
06/06/2019 |
| MYBPC3 |
AD |
Limited |
08/06/2019 |
| MYH7 |
AD |
Limited |
08/06/2019 |
| LMNA |
AD |
Limited |
09/06/2019 |
| RYR2 |
AD |
Refuting |
07/19/2019 |
| TTN |
AD |
Disputing |
10/28/2025 |
| TNNC1 |
AD |
No known disease relationship |
09/13/2019 |
| TNNI3 |
AD |
No known disease relationship |
07/16/2019 |
| TNNT2 |
AD |
No known disease relationship |
07/16/2019 |
| TPM1 |
AD |
No known disease relationship |
09/13/2019 |
Long QT Syndrome
| Gene |
Inheritance |
ClinGen Classification |
Date |
| KCNQ1 |
AD |
Definitive (LQT1) |
09/25/2018 |
| KCNH2 |
AD |
Definitive (LQT2) |
09/25/2018 |
| SCN5A |
— |
(See SCN5A-related cardiac rhythm disorder) |
10/08/2025 |
| CALM1 |
AD |
Definitive |
09/25/2018 |
| CALM2 |
AD |
Definitive |
09/25/2018 |
| CALM3 |
AD |
Definitive |
09/25/2018 |
| TRDN |
AR |
Strong |
04/24/2020 |
| CAV3 |
AD |
Limited |
12/15/2020 |
| KCNJ2 |
AD |
Limited |
12/15/2020 |
| SCN4B |
AD |
Disputing |
09/25/2018 |
| KCNQ1 |
AD |
Strong (Short QT) |
10/27/2020 |
| KCNH2 |
AD |
Definitive (Short QT) |
08/03/2020 |
| KCNJ2 |
AD |
Moderate (Short QT) |
10/27/2020 |
Brugada Syndrome
| Gene |
Inheritance |
ClinGen Classification |
Date |
| SCN5A |
— |
Definitive (SCN5A-related cardiac rhythm disorder, broad) |
10/08/2025 |
| KCNH2 |
AD |
Disputing |
06/10/2025 |
| CACNA1C |
AD |
Disputing |
02/25/2025 |
| CACNB2 |
AD |
Disputing |
07/22/2025 |
| ABCC9 |
AD |
Disputing |
10/28/2025 |
| SCN10A |
AD |
Disputing |
09/10/2025 |
| HCN4 |
AD |
Disputing |
11/21/2017 |
| SCN1B |
AD |
Disputing |
11/21/2017 |
| SCN2B |
AD |
Disputing |
11/21/2017 |
| PKP2 |
AD |
Disputing |
11/21/2017 |
| TRPM4 |
AD |
Refuting |
12/16/2025 |
| SCN3B |
AD |
Refuting |
12/16/2025 |
CPVT
| Gene |
Inheritance |
ClinGen Classification |
Date |
| RYR2 |
AD |
Definitive (CPVT1) |
01/20/2021 |
| CASQ2 |
AR |
Definitive (CPVT2) |
01/20/2021 |
| CASQ2 |
AD |
Moderate (CPVT2) |
01/20/2021 |
| TECRL |
AR |
Definitive (CPVT3) |
01/20/2021 |
| TRDN |
AR |
Definitive (CPVT5) |
01/20/2021 |
| CALM1 |
AD |
Moderate |
06/17/2021 |
| CALM2 |
AD |
Moderate |
06/17/2021 |
| CALM3 |
AD |
Moderate |
06/17/2021 |
| PKP2 |
AD |
Disputing |
01/20/2021 |
| KCNJ2 |
AD |
Disputing |
01/20/2021 |
SCN5A — Broad Cardiac Rhythm Disorder Designation
| Gene |
Disease |
Inheritance |
ClinGen |
Date |
| SCN5A |
SCN5A-related cardiac rhythm disorder |
AD |
Definitive |
10/08/2025 |
| SCN5A |
Dilated cardiomyopathy 1E |
AD |
Definitive |
03/04/2026 |
| SCN5A |
ARVC |
AD |
Limited |
06/06/2019 |
| SCN3B |
Atrial fibrillation |
AD |
Disputing |
01/05/2026 |
Pulmonary Arterial Hypertension (PAH)
| Gene |
Inheritance |
ClinGen Classification |
Date |
| BMPR2 |
AD |
Definitive |
12/07/2020 |
| CAV1 |
AD |
Definitive |
07/30/2025 |
| ATP13A3 |
Semidominant |
Definitive |
11/09/2021 |
| EIF2AK4 |
AR |
Definitive (PVOD/PCH) |
12/02/2022 |
| AQP1 |
AD |
Limited |
12/18/2025 |
| ABCC8 |
AD |
Moderate |
03/12/2025 |
| BMP10 |
AD |
Limited |
10/18/2022 |
| BMPR1A |
— |
Disputing |
10/18/2022 |
| BMPR1B |
— |
Disputing |
10/18/2022 |
Additional Cardiovascular — Selected Genes
| Gene |
Disease |
Inheritance |
ClinGen |
Date |
| HCN4 |
Sick sinus syndrome 2 |
AD |
Definitive |
06/24/2025 |
| ACTN2 |
ACTN2-related cardiac and skeletal myopathy |
AD |
Definitive |
07/23/2025 |
| CACNA1C |
Timothy syndrome |
AD |
Definitive |
04/14/2023 |
| ACTA2 |
Multisystemic smooth muscle dysfunction |
AD |
Definitive |
01/24/2025 |
| BGN |
Meester-Loeys syndrome (X-linked aortopathy) |
X-linked |
Strong |
02/06/2026 |
Limitations of the Document
- ClinGen curations represent the consensus of gene curation expert panels (GCEPs) at the date of the report; classifications are subject to revision as evidence accumulates.
- "Disputing" does not always mean the gene is definitively non-causal — it reflects that current evidence is insufficient to confirm prior claims; some disputed genes may be reclassified as evidence grows.
- The file does not capture all gene-disease pairs for all cardiovascular diseases (some pairs lack ClinGen curation); absence of a pair does not mean absence of evidence.
- Dosage sensitivity scoring (haploinsufficiency/triplosensitivity) is separate from gene-disease validity and not systematically captured here.
- Clinical actionability data are available only for a subset of gene-disease pairs.
Key Concepts Mentioned
Key Entities Mentioned
- entities/HCM — definitive: MYBPC3/MYH7/TNNC1/TPM1/FHOD3/CSRP3/ALPK3/ACTC1; disputed: CALR3/MYH6/CASQ2/DSP/VCL/KCNQ1/ANKRD1
- entities/DCM — definitive: TTN/LMNA/MYH7/SCN5A/DES/FLNC/BAG3/RBM20/TNNC1/TNNT2; disputed: PKP2
- entities/ARVC — definitive: PKP2/DSG2/DSC2/TMEM43/DSP(ACM); refuting: RYR2/TNNC1/TNNI3/TNNT2/TPM1
- entities/Brugada-Syndrome — SCN5A only definitive; KCNH2/CACNA1C/ABCC9/SCN10A/TRPM4/SCN3B disputed/refuting
- entities/CPVT — definitive: RYR2/CASQ2/TECRL/TRDN; moderate: CALM1/2/3; disputed: PKP2/KCNJ2
- entities/Long-QT-Syndrome — definitive: KCNQ1/KCNH2/CALM1/2/3; strong: TRDN; disputed: SCN4B
- entities/Pulmonary-Hypertension — definitive: BMPR2/CAV1/ATP13A3/EIF2AK4
- entities/SCN5A — new broad designation: "SCN5A-related cardiac rhythm disorder" (definitive 10/2025)
- entities/PKP2 — ARVC definitive; DCM and CPVT disputed; BrS disputing
- entities/RYR2 — CPVT definitive; ARVC refuting; HCM limited; DCM limited
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