DES
Chr 2ADARdesmin
Also known as: CDCD3, CSM1, CSM2, LGMD1D, LGMD1E, LGMD2R
Desmin encodes a muscle-specific intermediate filament protein that forms filamentous networks connecting myofibrils to each other and to the plasma membrane in cardiac and skeletal muscle. Mutations cause desmin-related myopathy and myofibrillar myopathy type 1, presenting as familial cardiac and skeletal myopathy, dilated cardiomyopathy, distal myopathies, or scapuloperoneal syndrome through dominant-negative mechanisms. Inheritance is autosomal dominant or autosomal recessive.
Moderate evidence — consider for supplementary testing
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
DES · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Standard or Comprehensive Radiation Therapy in Treating Patients With Early-Stage Breast Cancer Previously Treated With Chemotherapy and Surgery
ACTIVE NOT RECRUITINGE-Mindfulness Approaches for Living After Breast Cancer
RECRUITINGTesting the Application of Mepitel Film During Radiation Therapy to Reduce Radiation Related Redness and Peeling in Breast Cancer Patients Following Mastectomy
ACTIVE NOT RECRUITINGFollow-up Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene
ACTIVE NOT RECRUITINGThe PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer
ACTIVE NOT RECRUITINGRamucirumab Plus Pembrolizumab vs Usual Care for Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer Following Immunotherapy, Pragmatica-Lung Study
ACTIVE NOT RECRUITINGBiopsychosocial Markers of Addiction in Opioid Users: an Integrated Approach
ACTIVE NOT RECRUITINGHormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)
ACTIVE NOT RECRUITINGIdentification of New Candidate Genes for Hereditary Predisposition to Uveal Melanoma
RECRUITINGTesting MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer
ACTIVE NOT RECRUITINGTepotinib Phase II in NSCLC Harboring MET Alterations (VISION)
ACTIVE NOT RECRUITINGGemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools