NM_000252.3(MTM1):c.591_594del (p.Tyr198fs) AND Severe X-linked myotubular myopathy

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Oct 2, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000146464.9

Allele description [Variation Report for NM_000252.3(MTM1):c.591_594del (p.Tyr198fs)]

NM_000252.3(MTM1):c.591_594del (p.Tyr198fs)

Gene:

MTM1:myotubularin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000252.3(MTM1):c.591_594del (p.Tyr198fs)

HGVS:

NC_000023.11:g.150641331_150641334del
NG_008199.1:g.77758_77761del
NM_000252.3:c.591_594delMANE SELECT
NM_001376906.1:c.591_594del
NM_001376907.1:c.480_483del
NM_001376908.1:c.591_594del
NP_000243.1:p.Tyr198fs
NP_000243.1:p.Tyr198fs
NP_001363835.1:p.Tyr198fs
NP_001363836.1:p.Tyr161fs
NP_001363837.1:p.Tyr198fs
LRG_839t1:c.591_594del
LRG_839:g.77758_77761del
LRG_839p1:p.Tyr198fs
NC_000023.10:g.149809802_149809805del
NC_000023.10:g.149809804_149809807del
NM_000252.2:c.591_594del

Protein change:

Y161fs

Links:

dbSNP: rs587783839

NCBI 1000 Genomes Browser:

rs587783839

Molecular consequence:

NM_000252.3:c.591_594del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001376906.1:c.591_594del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001376907.1:c.480_483del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001376908.1:c.591_594del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

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Mus musculus strain:129X1/SvJ; 129S1/SvImJ; DBA/2J; A/J
Mus musculus strain:129X1/SvJ; 129S1/SvImJ; DBA/2J; A/J
Celera Genomics used whole genome shotgun sequencing to sequence the mouse genome

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000193752	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2007)	Pathogenic (Feb 8, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004196469	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 2, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004298749	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9285787, 9305655, 10063835, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000193752

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2007)

Pathogenic
(Feb 8, 2013)

germline

clinical testing

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

SCV004196469

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 2, 2023)

unknown

clinical testing

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

SCV004298749

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 17, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

See all PubMed Citations (6)

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV000193752.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004196469.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV004298749.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 158985). This variant is also known as ‚àÜ643‚Äì646 ACTT. This premature translational stop signal has been observed in individual(s) with X-linked myotubular myopathy (PMID: 9285787). This sequence change creates a premature translational stop signal (p.Tyr198Leufs*51) in the MTM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTM1 are known to be pathogenic (PMID: 9305655, 10063835).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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Relating variation to medicine