MTM1 p.Ile568Val

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The c.1702A>G variant in MTM1 is a missense variant predicted to cause substitution of isoleucine by valine at amino acid 568. The highest population filtering allele frequency in gnomAD v4.1.0 is 0.00002629 (33/895101 alleles, 9 hemizygotes) in European (non-Finnish) population, which is higher than the ClinGen Congenital Myopathies VCEP threshold (≥0.000016) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.212, which is neither above nor below the thresholds predicting a damaging or benign impact on MTM1 function. In summary, this variant meets the criteria to be classified as benign for X-linked centronuclear myopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen Congenital Myopathies VCEP: BA1. (Congenital Myopathies VCEP specifications version 1; 8/7/2024) LINK:https://erepo.genome.network/evrepo/ui/classification/CA172597/MONDO:0018947/149

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000030 ( 0 hom. 9 hem. )

Consequence

MTM1
NM_000252.3 missense

Scores

Clinical Significance

Benign reviewed by expert panel B:3

Conservation

PhyloP100: 1.60

Publications

0 publications found

Variant links:

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: Myriad Women's Health, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen, Genomics England PanelApp

MTM1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000252.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

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

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTM1	NM_000252.3	MANE Select	c.1702A>G	p.Ile568Val	missense	Exon 15 of 15	NP_000243.1	Q13496-1
MTM1	NM_001376908.1		c.1702A>G	p.Ile568Val	missense	Exon 15 of 15	NP_001363837.1	Q13496-1
MTM1	NM_001376906.1		c.1699A>G	p.Ile567Val	missense	Exon 15 of 15	NP_001363835.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTM1	ENST00000370396.7	TSL:1 MANE Select	c.1702A>G	p.Ile568Val	missense	Exon 15 of 15	ENSP00000359423.3	Q13496-1
MTM1	ENST00000689314.1		c.1747A>G	p.Ile583Val	missense	Exon 16 of 16	ENSP00000510607.1	A0A8I5KZ76
MTM1	ENST00000866458.1		c.1747A>G	p.Ile583Val	missense	Exon 16 of 16	ENSP00000536517.1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

110829

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000491

AC:

AN:

183296

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000978

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1098164

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363526

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26396

American (AMR)

AF:

0.00

AC:

AN:

35204

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0000368

AC:

AN:

842086

Other (OTH)

AF:

0.0000217

AC:

AN:

46097

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000180

AC:

AN:

110829

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32995

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30413

American (AMR)

AF:

0.00

AC:

AN:

10367

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.00

AC:

AN:

3548

South Asian (SAS)

AF:

0.00

AC:

AN:

2610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

53015

Other (OTH)

AF:

0.00

AC:

AN:

1480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

Centronuclear myopathy (1)

not specified (1)

Severe X-linked myotubular myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.29

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.81

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.40

PhyloP100

1.6

PrimateAI

Benign

0.41

PROVEAN

Benign

0.36

REVEL

Benign

0.21

Sift

Benign

0.56

Sift4G

Benign

0.38

Varity_R

0.066

gMVP

0.33

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over