autosomal recessive limb-girdle muscular dystrophy type 2G

Summary

autosomal recessive limb-girdle muscular dystrophy type 2G (MONDO:0011170) is a disease caused by TCAP (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TCAP (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 58
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		16	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2G
Mondo ID	MONDO:0011170
MeSH	C566599
OMIM	601954
Orphanet	34514
DOID	DOID:0110281
SNOMED CT	720522001
UMLS	C1866008
MedGen	400895
GARD	0010471
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in TCAP · autosomal recessive limb-girdle muscular dystrophy caused by mutation in Tcap · LGMD2G · limb-girdle muscular dystrophy due to telethonin deficiency · limb-girdle muscular dystrophy, type 2G · muscular dystrophy, limb-girdle, autosomal recessive 7 · muscular dystrophy, limb-girdle, type 2G · TCAP autosomal recessive limb-girdle muscular dystrophy · Tcap autosomal recessive limb-girdle muscular dystrophy

Data availability: 58 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive limb-girdle muscular dystrophy › autosomal recessive limb-girdle muscular dystrophy type 2G

Related subtypes (31): epidermolysis bullosa simplex 5B, with muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2A, autosomal recessive limb-girdle muscular dystrophy type 2B, autosomal recessive limb-girdle muscular dystrophy type 2C, autosomal recessive limb-girdle muscular dystrophy type 2H, autosomal recessive limb-girdle muscular dystrophy type 2F, autosomal recessive limb-girdle muscular dystrophy type 2E, autosomal recessive limb-girdle muscular dystrophy type 2I, autosomal recessive limb-girdle muscular dystrophy type 2D, autosomal recessive limb-girdle muscular dystrophy type 2J, autosomal recessive limb-girdle muscular dystrophy type 2K, autosomal recessive limb-girdle muscular dystrophy type 2L, autosomal recessive limb-girdle muscular dystrophy type 2M, autosomal recessive limb-girdle muscular dystrophy type 2O, autosomal recessive limb-girdle muscular dystrophy type 2N, autosomal recessive limb-girdle muscular dystrophy type 2Q, autosomal recessive limb-girdle muscular dystrophy type 2P, autosomal recessive limb-girdle muscular dystrophy type 2T, autosomal recessive limb-girdle muscular dystrophy type R18, autosomal recessive limb-girdle muscular dystrophy type 2U, limb-girdle muscular dystrophy due to POMK deficiency, autosomal recessive limb-girdle muscular dystrophy type 2X, autosomal recessive limb-girdle muscular dystrophy type 2W, autosomal recessive limb-girdle muscular dystrophy type 2Y, autosomal recessive limb-girdle muscular dystrophy type 2R1, muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8, muscular dystrophy, limb-girdle, autosomal recessive 23, muscular dystrophy, limb-girdle, autosomal recessive 26, muscular dystrophy, limb-girdle, autosomal recessive 27, muscular dystrophy, limb-girdle, autosomal recessive 28, muscular dystrophy, limb-girdle, autosomal recessive 29

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

58 retrieved; paginated sample, class counts are floors:

26 uncertain significance, 12 conflicting classifications of pathogenicity, 7 likely pathogenic, 5 pathogenic/likely pathogenic, 3 likely benign, 2 benign/likely benign, 2 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
290645	NM_003673.4(TCAP):c.66G>A (p.Trp22Ter)	TCAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
446463	NM_003673.4(TCAP):c.90_91del (p.Ser31fs)	TCAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
448649	NM_003673.4(TCAP):c.26_33dup (p.Glu12fs)	TCAP	Pathogenic	criteria provided, multiple submitters, no conflicts
522598	NM_003673.4(TCAP):c.34dup (p.Glu12fs)	TCAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5525	NM_003673.4(TCAP):c.157C>T (p.Gln53Ter)	TCAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5526	NM_003673.4(TCAP):c.110_110+1del	TCAP	Pathogenic	criteria provided, multiple submitters, no conflicts
813977	NM_003673.4(TCAP):c.75G>A (p.Trp25Ter)	TCAP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180772	NM_003673.4(TCAP):c.14_15del (p.Glu5fs)	TCAP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
140582	NM_003673.4(TCAP):c.32C>A (p.Ser11Ter)	TCAP	Likely pathogenic	no assertion criteria provided
1687576	NM_003673.4(TCAP):c.110+1G>A	TCAP	Likely pathogenic	criteria provided, single submitter
202113	NM_003673.4(TCAP):c.110+5G>T	TCAP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
217014	NM_003673.4(TCAP):c.25_31dup (p.Ser11Ter)	TCAP	Likely pathogenic	criteria provided, single submitter
3897040	NM_003673.4(TCAP):c.110+1_110+5del	TCAP	Likely pathogenic	criteria provided, single submitter
4073562	NM_003673.4(TCAP):c.165del (p.Gln56fs)	TCAP	Likely pathogenic	criteria provided, single submitter
177939	NM_003673.4(TCAP):c.32C>T (p.Ser11Leu)	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
191776	NM_003673.4(TCAP):c.313G>C (p.Glu105Gln)	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
202108	NM_003673.4(TCAP):c.113G>T (p.Cys38Phe)	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
288969	NM_003673.4(TCAP):c.313G>A (p.Glu105Lys)	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323046	NM_003673.4(TCAP):c.111-13C>T	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
323047	NM_003673.4(TCAP):c.*76G>T	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44710	NM_003673.4(TCAP):c.458G>A (p.Arg153His)	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
44714	NM_003673.4(TCAP):c.60C>G (p.Ala20=)	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464947	NM_003673.4(TCAP):c.282C>T (p.Phe94=)	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
808258	NM_003673.4(TCAP):c.341A>G (p.Gln114Arg)	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
889706	NM_003673.4(TCAP):c.*54G>A	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
891260	NM_003673.4(TCAP):c.*395C>T	TCAP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1019345	NM_003673.4(TCAP):c.457C>A (p.Arg153Ser)	TCAP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1023093	NM_003673.4(TCAP):c.194C>T (p.Pro65Leu)	TCAP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1026939	NM_003673.4(TCAP):c.478A>G (p.Met160Val)	TCAP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1036986	NM_003673.4(TCAP):c.294_295delinsAG (p.Met99Val)	TCAP	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TCAP	Strong	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2G	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TCAP	Orphanet:154	Familial isolated dilated cardiomyopathy
TCAP	Orphanet:34514	Telethonin-related limb-girdle muscular dystrophy R7

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TCAP	HGNC:11610	ENSG00000173991	O15273	Telethonin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TCAP	Telethonin	Muscle assembly regulating factor.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TCAP	Other/Unknown	no		Telethonin, Titin-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
hindlimb stylopod muscle	1
skeletal muscle tissue of rectus abdominis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TCAP	213	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TCAP	1,414

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TCAP	O15273	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Striated Muscle Contraction	1	308.6×	0.006	TCAP
Muscle contraction	1	77.2×	0.013	TCAP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
skeletal muscle myosin thick filament assembly	1	5617.3×	0.002	TCAP
sarcomerogenesis	1	5617.3×	0.002	TCAP
skeletal muscle thin filament assembly	1	2808.7×	0.002	TCAP
detection of muscle stretch	1	2407.4×	0.002	TCAP
otic vesicle formation	1	2106.5×	0.002	TCAP
cardiac muscle hypertrophy	1	1685.2×	0.002	TCAP
cardiac muscle tissue morphogenesis	1	1404.3×	0.002	TCAP
cardiac myofibril assembly	1	1296.3×	0.002	TCAP
adult heart development	1	1203.7×	0.002	TCAP
detection of mechanical stimulus	1	1203.7×	0.002	TCAP
cardiac muscle hypertrophy in response to stress	1	1053.2×	0.002	TCAP
muscle filament sliding	1	1053.2×	0.002	TCAP
response to muscle stretch	1	766.0×	0.002	TCAP
cardiac muscle cell development	1	624.1×	0.002	TCAP
skeletal muscle contraction	1	510.7×	0.002	TCAP
cardiac muscle contraction	1	401.2×	0.003	TCAP
sarcomere organization	1	383.0×	0.003	TCAP
somitogenesis	1	374.5×	0.003	TCAP
protein-containing complex assembly	1	113.9×	0.009	TCAP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TCAP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TCAP

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TCAP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments