Desminopathy: genes and variants
Explore variant evidence for Desminopathy across 4 analyzed proteins (DES, FLNC, BAG3, LDB3). Linked ClinVar records include 50 pathogenic or likely pathogenic variants, 2,721 variants of uncertain significance and 447 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-10. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Desminopathy
DES: Desmin
Its desmin filaments mechanically integrate sarcomeres with the nucleus, mitochondria, and cell junctions in striated muscle. Pathogenic variants cause desmin-related myopathy and can produce cardiomyopathy, conduction disease, and skeletal-muscle weakness.
37 ClinVar pathogenic / likely pathogenic and 475 uncertain variants in DES have source records linked to Desminopathy. Association strength is not clinical gene validity.
FLNC: Filamin-C
It crosslinks actin and anchors signaling and structural proteins at Z-discs, costameres, and other mechanically stressed sites in striated muscle. Pathogenic variants can cause arrhythmogenic or dilated cardiomyopathy as well as myofibrillar and distal myopathies.
7 ClinVar pathogenic / likely pathogenic and 1,710 uncertain variants in FLNC have source records linked to Desminopathy. Association strength is not clinical gene validity.
BAG3: BAG family molecular chaperone regulator 3
It coordinates chaperone-assisted protein quality control and autophagy, particularly in mechanically stressed cardiac and skeletal muscle. Pathogenic variants can impair sarcomere maintenance and cause dilated cardiomyopathy or myofibrillar myopathy.
5 ClinVar pathogenic / likely pathogenic and 527 uncertain variants in BAG3 have source records linked to Desminopathy. Association strength is not clinical gene validity.
LDB3: LIM domain-binding protein 3
It organizes Z-disc protein complexes and helps maintain sarcomere integrity during repeated muscle contraction. Pathogenic variants can cause myofibrillar myopathy and dilated or other forms of cardiomyopathy.
1 ClinVar pathogenic / likely pathogenic and 456 uncertain variants in LDB3 have source records linked to Desminopathy. Association strength is not clinical gene validity.
Where Desminopathy variants cluster
- DES Interaction with NEB (positions 268–415): 22 of 37 ClinVar pathogenic / likely pathogenic variants, 1.9× more than its size predicts.
- DES Coil 1A (positions 109–141): 6 of 37 ClinVar pathogenic / likely pathogenic variants, 2.3× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Desminopathy
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| BAG3 P209S | 209 | Pathogenic / likely pathogenic (★★) | |
| BAG3 P209L | 209 | Pathogenic / likely pathogenic (★★) | |
| DES E401D | 401 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES E401G | 401 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES K449T | 449 | Interaction with CRYAB | Pathogenic / likely pathogenic (★★) |
| DES N116S | 116 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES A120P | 120 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES L338R | 338 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES L345P | 345 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES R406W | 406 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES S12F | 12 | Head | Pathogenic / likely pathogenic (★★) |
| DES L377P | 377 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES H384R | 384 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES R454W | 454 | Tail | Pathogenic / likely pathogenic (★★) |
| LDB3 A145T | 145 | Pathogenic / likely pathogenic (★★) | |
| BAG3 E455K | 455 | BAG | Pathogenic / likely pathogenic (★★) |
| BAG3 P470S | 470 | BAG | Pathogenic / likely pathogenic (★★) |
| DES S2I | 2 | Head | Pathogenic / likely pathogenic (★★) |
| DES S13F | 13 | Head | Pathogenic / likely pathogenic (★★) |
| DES E245D | 245 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES R350P | 350 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES L370P | 370 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES E413K | 413 | IF rod | Pathogenic / likely pathogenic (★★) |
| DES P419S | 419 | Tail | Pathogenic / likely pathogenic (★★) |
| FLNC M222V | 222 | Calponin-homology (CH) 2 | Pathogenic / likely pathogenic (★★) |
| FLNC A1186V | 1186 | Filamin 10 | Pathogenic / likely pathogenic (★★) |
| FLNC V2297M | 2297 | Filamin 20 | Pathogenic / likely pathogenic (★★) |
| DES T442I | 442 | Interaction with CRYAB | Pathogenic / likely pathogenic (★★) |
| DES L115F | 115 | IF rod | Pathogenic / likely pathogenic (★) |
| DES L115I | 115 | IF rod | Pathogenic / likely pathogenic (★) |
| DES L338P | 338 | IF rod | Pathogenic / likely pathogenic (★) |
| BAG3 P209Q | 209 | Pathogenic / likely pathogenic (★) | |
| DES E401K | 401 | IF rod | Pathogenic / likely pathogenic (★) |
| DES R127C | 127 | IF rod | Pathogenic / likely pathogenic (★) |
| FLNC G1424V | 1424 | Filamin 12 | Pathogenic / likely pathogenic (★) |
| DES A120D | 120 | IF rod | Pathogenic / likely pathogenic (★) |
| DES Q348P | 348 | IF rod | Pathogenic / likely pathogenic (★) |
| DES R406P | 406 | IF rod | Pathogenic / likely pathogenic (★) |
| DES R383P | 383 | IF rod | Pathogenic / likely pathogenic (★) |
| DES L274P | 274 | IF rod | Pathogenic / likely pathogenic (★) |
| DES N342D | 342 | IF rod | Pathogenic / likely pathogenic (★) |
| DES L352S | 352 | IF rod | Pathogenic / likely pathogenic (★) |
| FLNC G1546D | 1546 | Filamin 14 | Pathogenic / likely pathogenic (★) |
| FLNC A1895P | 1895 | Filamin 17 | Pathogenic / likely pathogenic (★) |
| DES M1T | 1 | Pathogenic / likely pathogenic (★) | |
| DES A317P | 317 | IF rod | Pathogenic / likely pathogenic (★) |
| FLNC V2328M | 2328 | Filamin 21 | Pathogenic / likely pathogenic (★) |
| DES A285V | 285 | IF rod | Pathogenic / likely pathogenic |
| DES A360P | 360 | IF rod | Pathogenic / likely pathogenic |
| DES Q389P | 389 | IF rod | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Desminopathy
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| DES R383H | 383 | IF rod | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R383P at the same position is pathogenic; REVEL 0.832 |
| DES R350W | 350 | IF rod | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; R350P at the same position is pathogenic; REVEL 0.853 |
| DES L115P | 115 | IF rod | Uncertain (★) | +6: 3 other pathogenic changes within 3 positions; L115F at the same position is pathogenic; REVEL 0.992 |
| DES R350Q | 350 | IF rod | Uncertain (★★) | +6: 3 other pathogenic changes within 3 positions; R350P at the same position is pathogenic; REVEL 0.813 |
| DES R383C | 383 | IF rod | Uncertain (★★) | +6: 2 other pathogenic changes within 3 positions; R383P at the same position is pathogenic; REVEL 0.777 |
Which prediction tools work for Desminopathy
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- MutPred2: 94 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 93 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 93 out of 100
- REVEL: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 89 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 86 out of 100
- SIFT: 85 out of 100
- MetaLR: 82 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 74 out of 100
Same protein, different disease
- Hypertrophic cardiomyopathy also has ClinVar records linked to FLNC variants; they fall mostly in different places as the Desminopathy variants (10 pathogenic / likely pathogenic).
- Distal myopathy with posterior leg and anterior hand involvement also has ClinVar records linked to FLNC variants; they fall mostly in different places as the Desminopathy variants (9 pathogenic / likely pathogenic).
- Restrictive cardiomyopathy also has ClinVar records linked to FLNC variants; they fall mostly in different places as the Desminopathy variants (3 pathogenic / likely pathogenic).
- Dilated cardiomyopathy also has ClinVar records linked to LDB3 variants; they fall mostly in different places as the Desminopathy variants (4 pathogenic / likely pathogenic).
Diseases related to Desminopathy
- Dilated cardiomyopathy, also linked to BAG3, DES, FLNC and LDB3
- Cardiomyopathy, also linked to BAG3, DES, FLNC and LDB3
- Hypertrophic cardiomyopathy, also linked to BAG3, FLNC and LDB3
- Primary familial dilated cardiomyopathy, also linked to DES and LDB3
- Familial isolated dilated cardiomyopathy, also linked to BAG3 and DES
- Arrhythmogenic right ventricular dysplasia, also linked to DES
- Primary dilated cardiomyopathy, also linked to DES
- Left ventricular noncompaction, also linked to LDB3
- Distal myopathy with posterior leg and anterior hand involvement, also linked to FLNC
- Restrictive cardiomyopathy, also linked to FLNC
- Dilated cardiomyopathy 1HH, also linked to BAG3
- Myopathy, also linked to FLNC
Frequently asked questions
Which genes have records linked to Desminopathy?
This view contains 4 analyzed proteins: DES, FLNC, BAG3, LDB3. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 50 pathogenic or likely pathogenic variants, 2,721 variants of uncertain significance and 447 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 5 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 3,430 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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