MTM1
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
MTM1 (HGNC:7448) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
myotubularin 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
12.54(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.18(Read more about gnomAD LOEUF score)
Cytoband
Xq28
Genomic Coordinates
GRCh37/hg19: chrX:149737071-149841616 NCBI Ensembl UCSC
GRCh38/hg38: chrX:150562653-150673143 NCBI Ensembl UCSC
MANE Select Transcript
NM_000252.3 ENST00000370396.7 (Read more about MANE Select)
Function
Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) (PubMed:11001925, PubMed:10900271, PubMed:12646134, PubMed:14722070). Has also been shown to dephosphorylate phosphotyrosine- and phosphoserine-containing peptides (PubMed:9537414). Negatively regulates EGFR degradation through regulation of EGFR trafficking from the late endosome to the lysosome (PubMed:14722070). Plays a role in vacuolar formation and morph... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-11551
ClinGen Curation ID:
CCID:007493
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
01/11/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 10790201
    Laporte et al 2000 reported 29 variants in novel cases, including 16 variants not described before. Among these, 14 are clearly deleterious mutations that predict a truncated protein (nonsense and frameshift). Three changes affect essential nucleotides for the donor splice site, and the common FIQ420-421ins was found in two patients. To date, 198 variants have been identified in unrelated families, accounting for 133 different disease-associated variants which are widespread throughout the MTM1 gene. Most single-nucleotide variants are truncating, while 26% (35/133) are missense variants affecting residues conserved in the Drosophila ortholog and in the homologous MTMR1 gene. While most truncating mutations cause the severe and early lethal phenotype, some missense mutations are associated with milder forms and prolonged survival (up to 54 years).
  • PUBMED: 11793470
    Herman et al 2002 reported variants detected in 50 additional U.S. families with biopsy-proven MTM1. Forty-one of the patients have not been described previously, including 18 with novel mutations. 88% of the mothers of sporadic cases that were studied were identified as carriers, extending the previously reported high-carrier frequency for this disorder. Among the variants detected, 16 were missense, 9 were nonsense, 12 were splicing variants, 10 were small deletion/insertions, and 3 were large deletions.
  • PUBMED: 12522554
    Biancalana et al 2003 reported additional variants of MTM1 in 77 patients, including 35 novel ones.
HI Evidence Comments:
Loss of function mutations in MTM1 cause X-linked myotubular myopathy, including frameshift, nonsense, splicing, and deletion mutations. 7% of all variants are deletions involving one or more exons and typically cause severe disease. Males are always affected. Female carriers are usually asymptomatic but there have been rare reports of symptomatic females due to skewed X-inactivation. PMID: 10790201, 11793470, 12522554, 15145343, 15725586. See Gene Reviews.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
There are a couple of publications about the duplication of a part of MTM1 is also causing X-linked myotubular myopathy, but they didn’t encompass the whole gene (PMID 22968136, 22153990). One case report described a patient with a duplication almost cover the whole MTM1 gene, but it also harbors another gene, MAMLD1 (PMID 23273872).
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)