Myofibrillar myopathy 10

Summary

Myofibrillar myopathy 10 (MONDO:0033620) is a disease caused by SVIL (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SVIL (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myofibrillar myopathy 10
Mondo ID	MONDO:0033620
OMIM	619040
DOID	DOID:0112108
UMLS	C5436656
MedGen	1769385
GARD	0025814
Is cancer (heuristic)	no

Also known as: MFM10

Data availability: 12 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › congenital myopathy › congenital structural myopathy › myofibrillar myopathy › myofibrillar myopathy 10

Related subtypes (12): central core myopathy, myofibrillar myopathy 1, myofibrillar myopathy 3, myofibrillar myopathy 4, myofibrillar myopathy 5, myofibrillar myopathy 6, fatal infantile hypertonic myofibrillar myopathy, myofibrillar myopathy 7, myofibrillar myopathy 8, myofibrillar myopathy 11, myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy, myopathy, myofibrillar, 13, with rimmed vacuoles

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

12 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 3 likely pathogenic, 2 benign/likely benign, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
981487	NM_021738.3(SVIL):c.4812C>A (p.Tyr1604Ter)	SVIL	Pathogenic	no assertion criteria provided
981488	NM_021738.3(SVIL):c.3578_3579del (p.Val1193fs)	SVIL	Pathogenic	no assertion criteria provided
4845670	NM_021738.3(SVIL):c.820C>T (p.Arg274Ter)	SVIL	Likely pathogenic	criteria provided, single submitter
4845896	NM_021738.3(SVIL):c.3164-2A>G	SVIL	Likely pathogenic	criteria provided, single submitter
4849290	NM_021738.3(SVIL):c.2065C>T (p.Arg689Ter)	SVIL	Likely pathogenic	criteria provided, single submitter
1698787	NM_021738.3(SVIL):c.1783G>A (p.Ala595Thr)	SVIL	Uncertain significance	criteria provided, single submitter
1698922	NM_021738.3(SVIL):c.3386A>G (p.Glu1129Gly)	SVIL	Uncertain significance	criteria provided, single submitter
2361568	NM_021738.3(SVIL):c.1631G>A (p.Arg544His)	SVIL	Uncertain significance	criteria provided, multiple submitters, no conflicts
2442114	NM_021738.3(SVIL):c.3599C>T (p.Thr1200Met)	SVIL	Uncertain significance	criteria provided, single submitter
4686026	NM_021738.3(SVIL):c.2506C>T (p.Arg836Trp)	SVIL	Uncertain significance	criteria provided, single submitter
1264118	NM_021738.3(SVIL):c.6133+15G>A	SVIL	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
786582	NM_021738.3(SVIL):c.4241G>C (p.Ser1414Thr)	SVIL	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
SVIL	Strong	Autosomal recessive	myofibrillar myopathy 10	3

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
SVIL	HGNC:11480	ENSG00000197321	O95425	Supervillin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SVIL	Supervillin	Forms a high-affinity link between the actin cytoskeleton and the membrane.

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)
SVIL	Other/Unknown	no		Villin_headpiece, Villin/Gelsolin, Gelsolin-like_dom

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
gluteal muscle	1
skeletal muscle tissue of rectus abdominis	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SVIL	276	ubiquitous	marker	gluteal muscle, skeletal muscle tissue of rectus abdominis, vastus lateralis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SVIL	1,728

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SVIL	O95425	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
actin filament severing	1	1203.7×	0.002	SVIL
barbed-end actin filament capping	1	802.5×	0.002	SVIL
actin polymerization or depolymerization	1	766.0×	0.002	SVIL
positive regulation of cytokinesis	1	401.2×	0.003	SVIL
skeletal muscle tissue development	1	290.6×	0.003	SVIL

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
SVIL	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	SVIL

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)
SVIL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.