NM_000252.3(MTM1):c.679-1G>A AND Severe X-linked myotubular myopathy

Clinical significance:Likely pathogenic (Last evaluated: May 25, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000011805.14

Allele description [Variation Report for NM_000252.3(MTM1):c.679-1G>A]

NM_000252.3(MTM1):c.679-1G>A

Gene:
MTM1:myotubularin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000252.3(MTM1):c.679-1G>A
HGVS:
  • NC_000023.11:g.150645682G>A
  • NG_008199.1:g.82109G>A
  • NM_000252.2:c.679-1G>A
  • NM_000252.3:c.679-1G>AMANE SELECT
  • NM_001376906.1:c.679-1G>A
  • NM_001376907.1:c.568-1G>A
  • NM_001376908.1:c.679-1G>A
  • LRG_839t1:c.679-1G>A
  • LRG_839:g.82109G>A
  • NC_000023.10:g.149814155G>A
Nucleotide change:
IVS8, G-A, -1
Links:
OMIM: 300415.0004; dbSNP: rs672601324
NCBI 1000 Genomes Browser:
rs672601324
Molecular consequence:
  • NM_000252.2:c.679-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_000252.3:c.679-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001376906.1:c.679-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001376907.1:c.568-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001376908.1:c.679-1G>A - 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
SCV000032038OMIMno assertion criteria providedPathogenic
(Jan 1, 1998)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000949769Invitaecriteria provided, single submitter
Likely pathogenic
(May 25, 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
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Confirmation of prenatal diagnosis results of X-linked recessive myotubular myopathy by mutational screening, and description of three new mutations in the MTM1 gene.

Tanner SM, Laporte J, Guiraud-Chaumeil C, Liechti-Gallati S.

Hum Mutat. 1998;11(1):62-8.

PubMed [citation]
PMID:
9450905

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
See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000032038.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a family with X-linked myotubular myopathy (CNMX; 310400), Tanner et al. (1998) identified a G-to-A transition in the acceptor splice site of intron 8 (at nucleotide 733-1).

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

From Invitae, SCV000949769.3

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

Description

This sequence change affects an acceptor splice site in intron 8 of the MTM1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with X-linked centronuclear myopathy (PMID: 9305655). This variant is also known as G(733-1)A in the literature. ClinVar contains an entry for this variant (Variation ID: 11056). 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 30, 2021

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