# NM_004006.2(DMD):c.(?_32)_(649_?)del

https://sugi.bio/variant/dmd-c-32

## Summary

**DMD c.(?_32** is classified **Pathogenic** in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2016-08-19). Associated with muscular dystrophy.

**At a glance:** Pathogenic · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the DMD gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to muscular dystrophy.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Clinical trials | 132 registered for this condition — see ClinicalTrials.gov |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0007922/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DMD](https://sugi.bio/atlas/gene/DMD/) |
| Coding change (HGVS c.) | c.(?_32 |
| MANE Select transcript | [NM_004006](https://www.ncbi.nlm.nih.gov/nuccore/NM_004006) |
| Variant type | Deletion |
| Location | chrX:None-None (GRCh38) |
| ClinVar | [VCV505317](https://www.ncbi.nlm.nih.gov/clinvar/variation/505317/) |

**All HGVS expressions:** `LRG_199t1:c.(?_32)_(649_?)del`, `NC_000023.10:g.(?_32827610)_(33038317_?)del`, `NC_000023.11:g.(?_32809493)_(33020200_?)del`, `NM_004006.2:c.(?_32)_(649_?)del`

## Gene constraint & dosage {#gene-context}

**DMD** population constraint: ClinGen dosage — haploinsufficiency 3, triplosensitivity 0 (0–3 scale). *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **progressive muscular dystrophy** — Definitive (XL)

## Protein context {#protein}


**6 experimental structure(s)** (PDB): [1DXX](https://www.rcsb.org/structure/1DXX), [1EG3](https://www.rcsb.org/structure/1EG3), [1EG4](https://www.rcsb.org/structure/1EG4), [3UUN](https://www.rcsb.org/structure/3UUN), [9D58](https://www.rcsb.org/structure/9D58), [9EC1](https://www.rcsb.org/structure/9EC1).

## What this gene does {#gene-function}

*Describes the biological roles of DMD (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** DMD's established molecular role includes dystroglycan binding.


### Pathways affected {#pathways}

DMD participates in **3 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Striated Muscle Contraction](https://reactome.org/content/detail/R-HSA-390522) | curated |
| [Formation of the dystrophin-glycoprotein complex (DGC)](https://reactome.org/content/detail/R-HSA-9913351) | electronic |
| [Non-integrin membrane-ECM interactions](https://reactome.org/content/detail/R-HSA-3000171) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** dystroglycan binding, actin binding, structural constituent of muscle, myosin binding, vinculin binding.

**Biological process:** regulation of heart rate, intracellular protein localization, positive regulation of neuron projection development, peptide biosynthetic process, positive regulation of neuron differentiation, cardiac muscle contraction.

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2016-08-19.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Pathogenic | criteria provided, single submitter | clinical testing | 2016-08-19 |

## Associated conditions {#conditions}

[muscular dystrophy](https://sugi.bio/atlas/disease/muscular-dystrophy/).

**Reported phenotype names (ClinVar):** Muscular dystrophy.

## Similar variants {#similar}

Related DMD variant pages (same residue, condition, or type): [DMD p.Thr1683fs](/variant/dmd-p-thr1683fs), [DMD p.Leu1424Ter](/variant/dmd-p-leu1424ter), [DMD p.Arg2524His](/variant/dmd-p-arg2524his), [DMD c.357+1G>A](/variant/dmd-c-357-plus-1g-a), [DMD c.1812+601A>G](/variant/dmd-c-1812-plus-601a-g), [DMD c.9225-1G>C](/variant/dmd-c-9225-minus-1g-c), [DMD p.Leu575Pro](/variant/dmd-p-leu575pro), [DMD c.1150-14_1158dup](/variant/dmd-c-1150-minus-14-1158dup).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 505317). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*