NM_000252.3(MTM1):c.1354-2A>T AND Severe X-linked myotubular myopathy

Clinical significance:Likely pathogenic (Last evaluated: Nov 15, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001239440.1

Allele description [Variation Report for NM_000252.3(MTM1):c.1354-2A>T]

NM_000252.3(MTM1):c.1354-2A>T

Gene:
MTM1:myotubularin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000252.3(MTM1):c.1354-2A>T
HGVS:
  • NC_000023.11:g.150660369A>T
  • NG_008199.1:g.96796A>T
  • NM_000252.3:c.1354-2A>TMANE SELECT
  • NM_001376906.1:c.1354-2A>T
  • NM_001376907.1:c.1243-2A>T
  • NM_001376908.1:c.1354-2A>T
  • LRG_839t1:c.1354-2A>T
  • LRG_839:g.96796A>T
  • NC_000023.10:g.149828842A>T
  • NM_000252.2:c.1354-2A>T
Molecular consequence:
  • NM_000252.3:c.1354-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001376906.1:c.1354-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001376907.1:c.1243-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001376908.1:c.1354-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Severe X-linked myotubular myopathy (CNMX)
Synonyms:
X-linked centronuclear myopathy; MYOTUBULAR MYOPATHY 1; Myotubular myopathy, X-linked
Identifiers:
MONDO: MONDO:0010683; MedGen: C0410203; Orphanet: 596; OMIM: 310400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001412315Invitaecriteria provided, single submitter
Likely pathogenic
(Nov 15, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Mutations in the MTM1 gene implicated in X-linked myotubular myopathy. ENMC International Consortium on Myotubular Myopathy. European Neuro-Muscular Center.

Laporte J, Guiraud-Chaumeil C, Vincent MC, Mandel JL, Tanner SM, Liechti-Gallati S, Wallgren-Pettersson C, Dahl N, Kress W, Bolhuis PA, Fardeau M, Samson F, Bertini E.

Hum Mol Genet. 1997 Sep;6(9):1505-11.

PubMed [citation]
PMID:
9305655
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001412315.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 12 of the MTM1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with MTM1-related conditions. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MTM1 are known to be pathogenic (PMID: 9305655, 10063835). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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