Is MTM1 p.Arg69fs (c.205_209del) pathogenic?

MTM1 p.Arg69fs (c.205209del) is classified Likely pathogenic in MTM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-24). Associated with X-linked myotubular myopathy.

What condition is associated with MTM1 p.Arg69fs (c.205_209del)?

MTM1 p.Arg69fs (c.205_209del) is associated with X-linked myotubular myopathy (ClinVar).

How is X-linked centronuclear myopathy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MTM1 p.Arg69fs

c.205_209del · VCV3896918

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

X-linked myotubular myopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: MTM1
Protein: p.Arg69fs
Coding: c.205_209del
MANE Select: NM_000252
Type: Deletion
Location: chrX:150598659 (GRCh38)
Structure: AlphaFold pLDDT 90.10
Residue 69: the gram domain; a UniProt-annotated variant site (in cnmx; mild; reduced response to pi5p and reduced binding to pi(3,5)p2; abolishes interaction with mtmr12); a UniProt-annotated variant site (in cnmx); a UniProt-annotated variant site (in cnmx; severe)

Full MTM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked myotubular myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked centronuclear myopathy (Orphanet):

Inheritance: X-linked recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (France)

Similar variants

MTM1 p.Arg69Cys Pathogenic ★★★ same residue
MTM1 p.Arg69Gly Pathogenic ★ same residue
MTM1 p.Arg69His Uncertain significance ★ ⚠ same residue
MTM1 c.141_144del Pathogenic ★★★ same condition
MTM1 p.His598fs Likely pathogenic ★★★ same condition
MTM1 c.1349_1353+4del Pathogenic ★★ same condition
MTM1 c.232-26_232-23del Pathogenic/Likely pathogenic ★★ same condition
MTM1 c.342_342+4del Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mtm1-p-arg69fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown