Congenital myasthenic syndrome 19

Summary

Congenital myasthenic syndrome 19 (MONDO:0014745) is a disease caused by COL13A1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: COL13A1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 65

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myasthenic syndrome 19
Mondo ID	MONDO:0014745
OMIM	616720
DOID	DOID:0110673
UMLS	C4225235
MedGen	897962
GARD	0016153
Is cancer (heuristic)	no

Also known as: CMS19 · COL13A1 congenital myasthenic syndrome · congenital myasthenic syndrome caused by mutation in COL13A1 · congenital myasthenic syndrome type 19 · myasthenic syndrome, congenital, 19 · myasthenic syndrome, congenital, type 19

Data availability: 65 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › postsynaptic congenital myasthenic syndrome › congenital myasthenic syndrome 19

Related subtypes (13): congenital myasthenic syndrome 10, congenital myasthenic syndrome 1A, congenital myasthenic syndrome 16, congenital myasthenic syndrome 8, congenital myasthenic syndrome 17, congenital myasthenic syndrome 2A, congenital myasthenic syndrome 2C, congenital myasthenic syndrome 3A, congenital myasthenic syndrome 3B, congenital myasthenic syndrome 3C, congenital myasthenic syndrome 9, congenital myasthenic syndrome 11, congenital myasthenic syndrome 4

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

65 retrieved; paginated sample, class counts are floors:

30 uncertain significance, 12 likely pathogenic, 9 pathogenic, 7 benign, 3 pathogenic/likely pathogenic, 2 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2429343	NM_001371909.1(C10orf67):c.1570+4090T>C	C10orf67	Pathogenic	criteria provided, single submitter
1184983	NM_001368882.1(COL13A1):c.1884_1886delinsCCCT (p.Ser629fs)	COL13A1	Pathogenic	no assertion criteria provided
1184984	NM_001368882.1(COL13A1):c.675C>G (p.Tyr225Ter)	COL13A1	Pathogenic	no assertion criteria provided
1184985	NM_001368882.1(COL13A1):c.1619del (p.Asn540fs)	COL13A1	Pathogenic	no assertion criteria provided
1324099	NM_001368882.1(COL13A1):c.709C>T (p.Arg237Ter)	COL13A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
218905	NM_001368882.1(COL13A1):c.1206del (p.Leu403fs)	COL13A1	Pathogenic	no assertion criteria provided
218906	NC_000010.11:g.69888305del	COL13A1	Pathogenic	no assertion criteria provided
280690	NM_001368882.1(COL13A1):c.648del (p.Gly217fs)	COL13A1	Pathogenic	criteria provided, multiple submitters, no conflicts
3680272	NM_001368882.1(COL13A1):c.769_803del (p.Ser257fs)	COL13A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
975954	NM_001368882.1(COL13A1):c.1138C>T (p.Gln380Ter)	COL13A1	Pathogenic	criteria provided, single submitter
977150	NM_001368882.1(COL13A1):c.513del (p.Gly172fs)	COL13A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
982128	NM_001368882.1(COL13A1):c.1559G>A (p.Gly520Asp)	COL13A1	Pathogenic	criteria provided, single submitter
1066742	NM_001368882.1(COL13A1):c.1285-1G>C	COL13A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1504717	NM_001368882.1(COL13A1):c.967-2A>G	COL13A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1698998	NM_001368882.1(COL13A1):c.1026+1G>A	COL13A1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2412708	NM_001368882.1(COL13A1):c.803del (p.Pro268fs)	COL13A1	Likely pathogenic	criteria provided, single submitter
2664900	NM_001368882.1(COL13A1):c.457G>T (p.Glu153Ter)	COL13A1	Likely pathogenic	criteria provided, single submitter
2690570	NM_001368882.1(COL13A1):c.2022+1G>C	COL13A1	Likely pathogenic	criteria provided, single submitter
3896817	NM_001368882.1(COL13A1):c.512del (p.Pro171fs)	COL13A1	Likely pathogenic	criteria provided, single submitter
4056429	NM_001368882.1(COL13A1):c.685-1G>A	COL13A1	Likely pathogenic	criteria provided, single submitter
4845279	NM_001368882.1(COL13A1):c.646A>T (p.Lys216Ter)	COL13A1	Likely pathogenic	criteria provided, single submitter
4845280	NM_001368882.1(COL13A1):c.1339G>T (p.Gly447Ter)	COL13A1	Likely pathogenic	criteria provided, single submitter
4845842	NM_001368882.1(COL13A1):c.1231-2A>G	COL13A1	Likely pathogenic	criteria provided, single submitter
488484	NM_001368882.1(COL13A1):c.685-1164T>C	COL13A1	Likely pathogenic	criteria provided, single submitter
1033312	NM_001368882.1(COL13A1):c.750+18G>T	COL13A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1509144	NM_001368882.1(COL13A1):c.710G>A (p.Arg237Gln)	COL13A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031125	NM_001368882.1(COL13A1):c.567C>A (p.Asp189Glu)	COL13A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033311	NM_001368882.1(COL13A1):c.1610A>G (p.Lys537Arg)	COL13A1	Uncertain significance	criteria provided, single submitter
1039832	NM_001368882.1(COL13A1):c.1859G>A (p.Arg620His)	COL13A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1353231	NM_001368882.1(COL13A1):c.112C>T (p.Arg38Trp)	COL13A1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
COL13A1	Strong	Autosomal recessive	congenital myasthenic syndrome 19	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL13A1	Orphanet:98913	Postsynaptic congenital myasthenic syndrome
COL13A1	Orphanet:98914	Presynaptic congenital myasthenic syndromes

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL13A1	HGNC:2190	ENSG00000197467	Q5TAT6	Collagen alpha-1(XIII) chain	gencc,clinvar
C10orf67	HGNC:28716	ENSG00000179133	Q8IYJ2	Uncharacterized protein C10orf67, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL13A1	Collagen alpha-1(XIII) chain	Involved in cell-matrix and cell-cell adhesion interactions that are required for normal development.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL13A1	Other/Unknown	no		Collagen, Collagen_Structural_Proteins
C10orf67	Other/Unknown	no		DUF4709, DUF4724, C10orf67-like

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
cerebellum	1
buccal mucosa cell	1
right uterine tube	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL13A1	209	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, cerebellum
C10orf67	137	tissue_specific	marker	buccal mucosa cell, tendon of biceps brachii, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL13A1	1,308
C10orf67	177

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C10orf67	Q8IYJ2	71.37
COL13A1	Q5TAT6	55.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 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
Collagen chain trimerization	1	259.6×	0.007	COL13A1
Collagen degradation	1	175.7×	0.007	COL13A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL13A1
Integrin cell surface interactions	1	134.3×	0.007	COL13A1

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
morphogenesis of a branching structure	1	2106.5×	0.002	COL13A1
endochondral ossification	1	543.6×	0.005	COL13A1
cell-matrix adhesion	1	163.6×	0.010	COL13A1
cell-cell adhesion	1	101.5×	0.012	COL13A1
cell differentiation	1	29.1×	0.034	COL13A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
COL13A1	0	0
C10orf67	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	COL13A1, C10orf67

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL13A1	0	—
C10orf67	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.