# NM_002294.2(LAMP2):c.(?_929)_(1233_?)del

https://sugi.bio/variant/lamp2-c-929

## Summary

**LAMP2 c.(?_929** is classified **Likely pathogenic** in LAMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-03-24). Associated with Danon disease.

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

## For patients & families {#patients}

This is a change in the LAMP2 gene that is considered likely disease-causing, submitted by 1 submitter, and is linked to Danon disease.

*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.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | X-linked dominant |
| Age of onset (of this condition) | Childhood |
| Clinical trials | 7 registered for this condition — see ClinicalTrials.gov |
| Diagnostic panels | LAMP2 is a diagnostic-grade gene on 19 Genomics England panels |

**Commonly reported features of Danon disease** (across patients with this condition; presentation varies — frequencies from Orphanet):

- Intellectual disability — Very frequent (99-80%)
- Gait disturbance — Very frequent (99-80%)
- Hypertrophic cardiomyopathy — Very frequent (99-80%)
- Dilated cardiomyopathy — Very frequent (99-80%)
- Cardiorespiratory arrest — Very frequent (99-80%)
- Muscle flaccidity — Very frequent (99-80%)

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0009730/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [LAMP2](https://sugi.bio/atlas/gene/LAMP2/) |
| Coding change (HGVS c.) | c.(?_929 |
| MANE Select transcript | [NM_002294](https://www.ncbi.nlm.nih.gov/nuccore/NM_002294) |
| Variant type | Deletion |
| Location | chrX:None-None (GRCh38) |
| ClinVar | [VCV179651](https://www.ncbi.nlm.nih.gov/clinvar/variation/179651/) |

**All HGVS expressions:** `LRG_749t1:c.(?_929)_(1233_?)del`, `NC_000023.10:g.(?_119565178)_(119575749_?)del`, `NC_000023.11:g.(?_120431323)_(120441894_?)del`, `NM_002294.2:c.(?_929)_(1233_?)del`

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

**LAMP2** population constraint: ClinGen dosage — haploinsufficiency 3/3, triplosensitivity 0/3. *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):

- **Danon disease** — Definitive (XL)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 83.54, 60% of residues very-high.

**2 experimental structure(s)** (PDB): [2MOF](https://www.rcsb.org/structure/2MOF), [2MOM](https://www.rcsb.org/structure/2MOM).

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

*Describes the biological roles of LAMP2 (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:** LAMP2's established molecular role includes ion channel inhibitor activity.


### Pathways affected {#pathways}

LAMP2 participates in **3 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Neutrophil degranulation](https://reactome.org/content/detail/R-HSA-6798695) | curated |
| [Platelet degranulation ](https://reactome.org/content/detail/R-HSA-114608) | curated |
| [Chaperone Mediated Autophagy](https://reactome.org/content/detail/R-HSA-9613829) | electronic |

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

**Molecular function:** ion channel inhibitor activity, enzyme binding, protein-macromolecule adaptor activity, signaling adaptor activity.

**Biological process:** lysosomal lumen acidification, protein catabolic process, negative regulation of protein-containing complex assembly, regulation of protein stability, chaperone-mediated autophagy, protein targeting to lysosome involved in chaperone-mediated autophagy.

## Clinical significance {#significance}

**Likely pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2014-03-24.

**Submitter consensus:** unanimous (1/1 Likely pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Likely pathogenic | criteria provided, single submitter | clinical testing | 2014-03-24 |

## Associated conditions {#conditions}

[Danon disease](https://sugi.bio/atlas/disease/danon-disease/).

**Reported phenotype names (ClinVar):** Danon disease, PSEUDOGLYCOGENOSIS II, Glycogen Storage Disease Type IIb, ANTOPOL DISEASE, GSD IIb, LYSOSOMAL GLYCOGEN STORAGE DISEASE WITHOUT ACID MALTASE DEFICIENCY.

## Similar variants {#similar}

Related LAMP2 variant pages (same residue, condition, or type): [LAMP2 c.864+3_864+6del](/variant/lamp2-c-864-plus-3-864-plus-6del), [LAMP2 p.Phe284fs](/variant/lamp2-p-phe284fs), [LAMP2 p.Ser155fs](/variant/lamp2-p-ser155fs), [LAMP2 p.Thr211fs](/variant/lamp2-p-thr211fs), [LAMP2 c.742-7_742-5del](/variant/lamp2-c-742-minus-7-742-minus-5del), [LAMP2 c.865-8del](/variant/lamp2-c-865-minus-8del), [LAMP2 c.183_183+4del](/variant/lamp2-c-183-183-plus-4del), [LAMP2 c.865-1_865del](/variant/lamp2-c-865-minus-1-865del).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); 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 2026-10-14); 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 179651). 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.*