Congenital myasthenic syndrome 7

Summary

Congenital myasthenic syndrome 7 (MONDO:0014468) is a disease caused by SYT2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SYT2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital myasthenic syndrome 7
Mondo ID	MONDO:0014468
OMIM	616040
DOID	DOID:0110659
UMLS	C4015038
MedGen	863475
GARD	0016053
Is cancer (heuristic)	no

Also known as: CMS7 · congenital myasthenic syndrome caused by mutation in SYT2 · congenital myasthenic syndrome type 7 · myasthenic syndrome, congenital, 7, presynaptic · myasthenic syndrome, congenital, 7A, presynaptic, and distal motor neuropathy, autosomal dominant · SYT2 congenital myasthenic syndrome

Data availability: 18 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › congenital myasthenic syndrome › presynaptic congenital myasthenic syndrome › congenital myasthenic syndrome 7

Related subtypes (9): congenital myasthenic syndrome 6, congenital myasthenic syndrome 8, congenital myasthenic syndrome 18, congenital myasthenic syndrome 19, congenital myasthenic syndrome 20, congenital myasthenic syndrome 21, myasthenic syndrome, congenital, 23, presynaptic, myasthenic syndrome, congenital, 24, presynaptic, myasthenic syndrome, congenital, 25, presynaptic

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

18 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 4 pathogenic, 2 benign/likely benign, 2 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1192311	NM_177402.5(SYT2):c.1112T>A (p.Ile371Lys)	SYT2	Pathogenic	no assertion criteria provided
1192312	NM_177402.5(SYT2):c.1082_1096del (p.Asp361_Leu365del)	SYT2	Pathogenic	no assertion criteria provided
1192313	NM_177402.5(SYT2):c.1094T>C (p.Leu365Pro)	SYT2	Pathogenic	criteria provided, single submitter
156368	NM_177402.5(SYT2):c.920A>C (p.Asp307Ala)	SYT2	Pathogenic	no assertion criteria provided
3064703	NM_177402.5(SYT2):c.548_549delinsGGA (p.Leu183fs)	SYT2	Likely pathogenic	criteria provided, single submitter
4278115	NM_177402.5(SYT2):c.1017G>C (p.Glu339Asp)	SYT2	Likely pathogenic	criteria provided, single submitter
156369	NM_177402.5(SYT2):c.923C>T (p.Pro308Leu)	SYT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1959486	NM_177402.5(SYT2):c.797_801+1del	SYT2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1030352	NM_177402.5(SYT2):c.199G>A (p.Ala67Thr)	SYT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1346883	NM_177402.5(SYT2):c.2T>A (p.Met1Lys)	SYT2	Uncertain significance	criteria provided, single submitter
1347310	NM_177402.5(SYT2):c.982G>A (p.Val328Met)	SYT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2444098	NM_177402.5(SYT2):c.1081G>A (p.Asp361Asn)	SYT2	Uncertain significance	criteria provided, single submitter
3892596	NM_177402.5(SYT2):c.378G>C (p.Glu126Asp)	SYT2	Uncertain significance	criteria provided, single submitter
931591	NM_177402.5(SYT2):c.358G>A (p.Ala120Thr)	SYT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
975873	NM_177402.5(SYT2):c.87del (p.Ser30fs)	SYT2	Uncertain significance	criteria provided, single submitter
1200856	NM_177402.5(SYT2):c.804G>A (p.Pro268=)	SYT2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1295576	NM_177402.5(SYT2):c.117C>T (p.Ser39=)	SYT2	Benign	criteria provided, multiple submitters, no conflicts
445706	NM_177402.5(SYT2):c.465+20_465+21del	SYT2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 1 · 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
SYT2	Strong	Autosomal dominant	congenital myasthenic syndrome 7	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SYT2	Orphanet:98914	Presynaptic congenital myasthenic syndromes

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
SYT2	HGNC:11510	ENSG00000143858	Q8N9I0	Synaptotagmin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SYT2	Synaptotagmin-2	Exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties.

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)
SYT2	Other/Unknown	no		C2_dom, Synaptotagmin, C2_domain_sf

Expression context

Cohort genes with no expression data: 0.

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
olfactory bulb	1
pons	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SYT2	165	tissue_specific	yes	olfactory bulb, pons, type B pancreatic cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SYT2	1,991

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SYT2	Q8N9I0	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Toxicity of botulinum toxin type B (botB)	1	3806.7×	0.003	SYT2
Neurotoxicity of clostridium toxins	1	1427.5×	0.005	SYT2
Uptake and actions of bacterial toxins	1	815.7×	0.005	SYT2
Bacterial Infection Pathways	1	335.9×	0.010	SYT2
Protein-protein interactions at synapses	1	265.6×	0.010	SYT2
Neurexins and neuroligins	1	196.9×	0.011	SYT2
Cargo recognition for clathrin-mediated endocytosis	1	104.8×	0.018	SYT2
Clathrin-mediated endocytosis	1	85.2×	0.019	SYT2
Neuronal System	1	44.3×	0.033	SYT2
Membrane Trafficking	1	37.1×	0.034	SYT2
Vesicle-mediated transport	1	34.8×	0.034	SYT2
Infectious disease	1	24.8×	0.044	SYT2
Disease	1	13.1×	0.076	SYT2

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
calcium-dependent activation of synaptic vesicle fusion	1	1296.3×	0.003	SYT2
regulation of calcium ion-dependent exocytosis	1	936.2×	0.003	SYT2
positive regulation of dendrite extension	1	732.7×	0.003	SYT2
regulation of synaptic vesicle exocytosis	1	455.5×	0.003	SYT2
vesicle-mediated transport	1	96.3×	0.012	SYT2
cell differentiation	1	29.1×	0.034	SYT2

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
SYT2	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	SYT2

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)
SYT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.