MTM1 p.Leu194Leu

Variant names:

• chrX-150641319-G-G
• NM_000252.3:c.

Your query was ambiguous. Multiple possible variants found:

• chrX-150641320--
• chrX-150641322-C-T
• chrX-150641322-C-A
• chrX-150641322-C-G
• chrX-150641320-CTC-TTA
• chrX-150641320-CTC-TTG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000252.3(MTM1):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene MTM1 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: not found (cov: 22)
• Consequence: MTM1 NM_000252.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

Genes affected

MTM1 (HGNC:7448): (myotubularin 1) This gene encodes a dual-specificity phosphatase that acts on both phosphotyrosine and phosphoserine. It is required for muscle cell differentiation and mutations in this gene have been identified as being responsible for X-linked myotubular myopathy. [provided by RefSeq, Jul 2008]

MTM1 Gene-Disease associations (from GenCC):

• X-linked myotubular myopathy

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, G2P, Orphanet, Genomics England PanelApp, Myriad Women's Health, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Specifications for MTM1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000252.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	NM_000252.3	MANE Select	c.		intron	N/A	NP_000243.1	Q13496-1
	MTM1	NM_001376908.1		c.		intron	N/A	NP_001363837.1	Q13496-1
	MTM1	NM_001376906.1		c.		intron	N/A	NP_001363835.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTM1	ENST00000370396.7	TSL:1 MANE Select	c.		intron	N/A	ENSP00000359423.3	Q13496-1
	MTM1	ENST00000689314.1		c.		intron	N/A	ENSP00000510607.1	A0A8I5KZ76
	MTM1	ENST00000866458.1		c.		intron	N/A	ENSP00000536517.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-149809792;