Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000252.3(MTM1):c.1792del (p.His598fs)

CA271849

158953 (ClinVar)

Gene: MTM1
Condition: X-linked centronuclear myopathy
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 74a6efa5-e446-4a1f-a18c-f9ad77167e3a
Approved on: 2024-08-07
Published on: 2024-10-01

HGVS expressions

NM_000252.3:c.1792del
NM_000252.3(MTM1):c.1792del (p.His598fs)
NC_000023.11:g.150671575del
CM000685.2:g.150671575del
NC_000023.10:g.149840048del
CM000685.1:g.149840048del
NC_000023.9:g.149590706del
NG_008199.1:g.108002del
ENST00000684910.1:c.*1325del
ENST00000685439.1:c.1447del
ENST00000685944.1:c.1792del
ENST00000686212.1:n.1394del
ENST00000687215.1:c.*1547del
ENST00000688152.1:c.*1236del
ENST00000688403.1:c.1048del
ENST00000689314.1:c.1837del
ENST00000689694.1:c.1792del
ENST00000689810.1:c.*1441del
ENST00000690282.1:c.1048del
ENST00000690351.1:c.*1444del
ENST00000691232.1:c.1447del
ENST00000691482.1:n.5755del
ENST00000691686.1:c.1699del
ENST00000691851.1:c.1201del
ENST00000692015.1:c.1579del
ENST00000692638.1:c.*1590del
ENST00000692852.1:c.1603del
ENST00000692915.1:c.*1938del
ENST00000370396.7:c.1792del
ENST00000306167.11:n.1656del
ENST00000370396.6:c.1792del
NM_000252.2:c.1792del
NM_001376906.1:c.1789del
NM_001376907.1:c.1681del
NM_001376908.1:c.1792del
More

Likely Pathogenic

Met criteria codes 4
PP4 PM4 PM2_Supporting PS4_Moderate
Not Met criteria codes 17
PS1 PS3 PP1 PP3 PP2 PM5 PM1 PVS1 BA1 BS2 BS4 BS3 BS1 BP7 BP4 BP1 BP3

Evidence Links 0

Expert Panel

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 NM_000252.3:c.1792del (p.His598Metfs*23) variant in MTM1 is a frameshift variant in the last exon (exon 15) whose frameshift is predicted to extend the myotubularin protein by 16 amino acids at its C terminus (PM4). The variant is absent from gnomAD v4.1.0 meeting PM2_Supporting. This variant has been detected in 3 individuals with centronuclear myopathy (PS4_Moderate, PMID:9931531, 31541013, 35729264), one of which was a female adult carrier with moderate MTM1-related myopathy showing distal muscle weakness, assisted ambulation, asymmetric muscle weakness, hemifacial hypoplasia, and differences in hand size which is highly specific for the condition (PP4, PMID:31541013). In summary, this variant meets the criteria to be classified as likely pathogenic for X-linked centronuclear myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: PS4_Moderate, PM4, PP4, PM2_Supporting (ClinGen Congenital Myopathies VCEP specifications version 1; 8/7/2024).
Met criteria codes
PP4
A female adult carrier with moderate MTM1-related myopathy had distal muscle weakness, assisted ambulation, asymmetric muscle weakness, hemifacial hypoplasia, and differences in hand size which is highly specific for the disease (PP4, PMID:31541013)
PM4
The frameshift variant in the last exon (exon 15) is predicted to extend the myotubularin protein by 16 amino acids at its C terminus (PM4)
PM2_Supporting
The variant is absent from gnomAD v4.1.0 meeting PM2_Supporting.
PS4_Moderate
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Not Met criteria codes
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
PM4 applied to the variant
BA1
The variant is absent from gnomAD v2.1.1
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
The variant is absent from gnomAD v2.1.1
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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