Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000252.3(MTM1):c.137-7T>G

CA271794

158926 (ClinVar)

Gene: MTM1

Condition: centronuclear myopathy

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 769d8526-5dc3-4b75-92ce-3bdfd376d493

Approved on: 2024-08-07

Published on: 2024-10-01

HGVS expressions

NM_000252.3:c.137-7T>G

NM_000252.3(MTM1):c.137-7T>G

NC_000023.11:g.150598585T>G

CM000685.2:g.150598585T>G

NC_000023.10:g.149767049T>G

CM000685.1:g.149767049T>G

NC_000023.9:g.149517707T>G

NG_008199.1:g.35003T>G

ENST00000684910.1:c.136+2015T>G

ENST00000685439.1:c.-3-20453T>G

ENST00000685944.1:c.137-7T>G

ENST00000687215.1:c.-149-7T>G

ENST00000687365.1:n.192-7T>G

ENST00000688152.1:c.137-7T>G

ENST00000688403.1:c.-301+29723T>G

ENST00000689314.1:c.137-7T>G

ENST00000689694.1:c.137-7T>G

ENST00000689810.1:c.137-7T>G

ENST00000690282.1:c.-301+29867T>G

ENST00000690351.1:c.136+2015T>G

ENST00000691232.1:c.-3-20453T>G

ENST00000691686.1:c.137-7T>G

ENST00000691851.1:c.137-7T>G

ENST00000692015.1:c.137-7T>G

ENST00000692638.1:c.136+2015T>G

ENST00000692852.1:c.137-7T>G

ENST00000692915.1:c.137-7T>G

ENST00000693422.1:n.198-7T>G

ENST00000370396.7:c.137-7T>G

ENST00000306167.11:n.176-7T>G

ENST00000370396.6:c.137-7T>G

ENST00000424519.1:c.137-7T>G

ENST00000490530.1:n.170+2015T>G

NM_000252.2:c.137-7T>G

NM_001376906.1:c.137-7T>G

NM_001376907.1:c.137-7T>G

NM_001376908.1:c.137-7T>G

Uncertain Significance

PM2_Supporting PP3

BS1 BP4 PS4 BA1

Evidence Links 0

Expert Panel

Congenital Myopathies VCEP

Criteria Specification Information

Criteria Specification: ClinGen Congenital Myopathies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MTM1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Congenital Myopathies VCEP

The c.137-7T>G variant in MTM1 is located in the 3’ non-canonical splice site of intron 3. This variant is absent from gnomAD v4.1.0 (PM2_Supporting). The computational predictor Splice AI gives a score of 0.55, which is above the threshold of 0.5, suggesting impact on splicing (PP3). In summary, this variant meets the criteria to be classified as uncertain significance for X-linked centronuclear myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: PM2_Supporting, PP3. (Congenital Myopathies VCEP specifications Version 1: 8/7/2024).

PM2_Supporting

This variant is absent from gnomAD v4.1.0

PP3

Splice AI gives a score of 0.55, which is above the threshold of 0.5, suggesting impact on splicing

BS1

This variant is absent from gnomAD v4.1.0

BP4

Splice AI gives a score of 0.55, which is above the threshold of 0.5, suggesting impact on splicing

PS4

One patient with moderate myotubular myopathy has been reported in a publication (PMID:11793470)

BA1

This variant is absent from gnomAD v4.1.0

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