PVS1, PM2, PP5
ClinVar Genomic variation as it relates to human health
NM_004006.3(DMD):c.10141C>T (p.Arg3381Ter)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(11)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic
11
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_004006.3(DMD):c.10141C>T (p.Arg3381Ter)
Variation ID: 11273 Accession: VCV000011273.41
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xp21.2 X: 31178751 (GRCh38) [ NCBI UCSC ] X: 31196868 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 19, 2015 Oct 20, 2024 May 1, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_004006.3:c.10141C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003997.2:p.Arg3381Ter nonsense NM_000109.4:c.10117C>T NP_000100.3:p.Arg3373Ter nonsense NM_004009.3:c.10129C>T NP_004000.1:p.Arg3377Ter nonsense NM_004010.3:c.9772C>T NP_004001.1:p.Arg3258Ter nonsense NM_004011.4:c.6118C>T NP_004002.3:p.Arg2040Ter nonsense NM_004012.4:c.6109C>T NP_004003.2:p.Arg2037Ter nonsense NM_004013.3:c.2761C>T NP_004004.2:p.Arg921Ter nonsense NM_004014.3:c.1954C>T NP_004005.2:p.Arg652Ter nonsense NM_004015.3:c.937C>T NP_004006.1:p.Arg313Ter nonsense NM_004016.3:c.937C>T NP_004007.1:p.Arg313Ter nonsense NM_004017.3:c.937C>T NP_004008.1:p.Arg313Ter nonsense NM_004018.3:c.937C>T NP_004009.1:p.Arg313Ter nonsense NM_004019.3:c.937C>T NP_004010.1:p.Arg313Ter nonsense NM_004020.4:c.2761C>T NP_004011.3:p.Arg921Ter nonsense NM_004021.3:c.2761C>T NP_004012.2:p.Arg921Ter nonsense NM_004022.3:c.2761C>T NP_004013.2:p.Arg921Ter nonsense NM_004023.3:c.2761C>T NP_004014.2:p.Arg921Ter nonsense NC_000023.11:g.31178751G>A NC_000023.10:g.31196868G>A NG_012232.1:g.2165859C>T LRG_199:g.2165859C>T LRG_199t1:c.10141C>T LRG_199p1:p.Arg3381Ter - Protein change
- R3381*, R3258*, R921*, R2040*, R313*, R2037*, R3373*, R3377*, R652*
- Other names
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NP_003997.1:p.Arg3381*
- Canonical SPDI
- NC_000023.11:31178750:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| DMD | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9359 | 9653 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 14, 2024 | RCV000012024.15 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
May 1, 2024 | RCV000437942.13 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 10, 2021 | RCV001813973.1 | |
|
Dystrophin deficiency
|
Pathogenic (1) |
no assertion criteria provided
|
Jan 30, 2018 | RCV001835626.1 |
|
See cases
|
Pathogenic (1) |
criteria provided, single submitter
|
Mar 8, 2021 | RCV002287331.1 |
|
X-linked DMD-related dystrophinopathy
|
Pathogenic (1) |
no assertion criteria provided
|
Aug 25, 2019 | RCV000985010.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Pathogenic
(Jun 23, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000112313.5
First in ClinVar: Jan 17, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 5
Sex: mixed
|
|
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Pathogenic
(Dec 16, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Duchenne muscular dystrophy
Affected status: yes
Allele origin:
germline
|
Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV002769640.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
PVS1, PM2, PP5
|
|
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Pathogenic
(Jan 14, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Duchenne muscular dystrophy
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000932937.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg3381*) in the DMD gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg3381*) in the DMD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with DMD-related muscular dystrophy (PMID: 8281150, 10320864, 27593222). ClinVar contains an entry for this variant (Variation ID: 11273). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
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Pathogenic
(Dec 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000516731.5
First in ClinVar: Mar 08, 2017 Last updated: Sep 16, 2024 |
Comment:
Reported previously in association with dystrophinopathy in published literature, the Leiden Open Variation Database, the UMD-DMD database and in individuals referred for genetic testing at … (more)
Reported previously in association with dystrophinopathy in published literature, the Leiden Open Variation Database, the UMD-DMD database and in individuals referred for genetic testing at GeneDx (PMID: 27425820, 8281150, 10320864, 19783145); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Based on the understanding of this genetic alteration, it may be amenable to nonsense read-through therapy that is currently available or in clinical trial; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19783145, 27425820, 27593222, 30833962, 23148581, 10320864, 25525159, 26886021, 20409719, 33773883, 32358784, 8281150) (less)
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Pathogenic
(May 01, 2024)
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criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV005051403.5
First in ClinVar: Jun 17, 2024 Last updated: Oct 20, 2024 |
Comment:
DMD: PVS1, PM2, PS4:Moderate
Number of individuals with the variant: 1
|
|
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Pathogenic
(Jun 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
(X-linked recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000255693.2
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2015
Comment:
X-linked recessive inheritance
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|
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Pathogenic
(Jul 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
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Abnormality of the musculature
Affected status: yes
Allele origin:
germline
|
Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV001755590.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
|
|
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Pathogenic
(Mar 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
see cases
Affected status: yes
Allele origin:
unknown
|
Institute of Human Genetics, University Hospital Muenster
Accession: SCV002578019.1
First in ClinVar: Oct 08, 2022 Last updated: Oct 08, 2022 |
Comment:
ACMG categories: PVS1,PM2,PP3,PP5
Number of individuals with the variant: 1
Clinical Features:
Myopathy (present) , Infantile muscular hypotonia (present) , Global developmental delay (present) , Elevated circulating creatine kinase concentration (present) , Spasticity (present) , Poor head … (more)
Myopathy (present) , Infantile muscular hypotonia (present) , Global developmental delay (present) , Elevated circulating creatine kinase concentration (present) , Spasticity (present) , Poor head control (present) (less)
Age: 0-9 years
Sex: male
Tissue: blood
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|
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Pathogenic
(Aug 25, 2019)
|
no assertion criteria provided
Method: clinical testing
|
X-linked DMD-related dystrophinopathy
Affected status: yes
Allele origin:
germline
|
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001132941.1
First in ClinVar: Jan 04, 2020 Last updated: Jan 04, 2020 |
|
|
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Pathogenic
(Jan 30, 2018)
|
no assertion criteria provided
Method: clinical testing
|
Becker muscular dystrophy
Cardiomyopathy Duchenne muscular dystrophy Dystrophin deficiency
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002077620.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
|
|
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Pathogenic
(Nov 01, 1993)
|
no assertion criteria provided
Method: literature only
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DUCHENNE MUSCULAR DYSTROPHY
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000032258.3
First in ClinVar: Apr 04, 2013 Last updated: Mar 18, 2023 |
Comment on evidence:
Lenk et al. (1993) identified a C-to-T substitution at position 10349 of the DMD gene, encoding a stop codon at position 3381, in a patient … (more)
Lenk et al. (1993) identified a C-to-T substitution at position 10349 of the DMD gene, encoding a stop codon at position 3381, in a patient with Duchenne muscular dystrophy (DMD; 310200). (less)
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Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Arg3381*) in the DMD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with DMD-related muscular dystrophy (PMID: 8281150, 10320864, 27593222). ClinVar contains an entry for this variant (Variation ID: 11273). For these reasons, this variant has been classified as Pathogenic.
Comment:
Reported previously in association with dystrophinopathy in published literature, the Leiden Open Variation Database, the UMD-DMD database and in individuals referred for genetic testing at GeneDx (PMID: 27425820, 8281150, 10320864, 19783145); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Based on the understanding of this genetic alteration, it may be amenable to nonsense read-through therapy that is currently available or in clinical trial; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19783145, 27425820, 27593222, 30833962, 23148581, 10320864, 25525159, 26886021, 20409719, 33773883, 32358784, 8281150)
Comment:
DMD: PVS1, PM2, PS4:Moderate
Comment:
ACMG categories: PVS1,PM2,PP3,PP5
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
PVS1, PM2, PP5
Comment:
This sequence change creates a premature translational stop signal (p.Arg3381*) in the DMD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with DMD-related muscular dystrophy (PMID: 8281150, 10320864, 27593222). ClinVar contains an entry for this variant (Variation ID: 11273). For these reasons, this variant has been classified as Pathogenic.
Comment:
Reported previously in association with dystrophinopathy in published literature, the Leiden Open Variation Database, the UMD-DMD database and in individuals referred for genetic testing at GeneDx (PMID: 27425820, 8281150, 10320864, 19783145); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Based on the understanding of this genetic alteration, it may be amenable to nonsense read-through therapy that is currently available or in clinical trial; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19783145, 27425820, 27593222, 30833962, 23148581, 10320864, 25525159, 26886021, 20409719, 33773883, 32358784, 8281150)
Comment:
DMD: PVS1, PM2, PS4:Moderate
Comment:
ACMG categories: PVS1,PM2,PP3,PP5
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Consecutive analysis of mutation spectrum in the dystrophin gene of 507 Korean boys with Duchenne/Becker muscular dystrophy in a single center. | Cho A | Muscle & nerve | 2017 | PMID: 27593222 |
| 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 | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
| New variants, challenges and pitfalls in DMD genotyping: implications in diagnosis, prognosis and therapy. | Santos R | Journal of human genetics | 2014 | PMID: 25007885 |
| Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort. | Flanigan KM | Human mutation | 2009 | PMID: 19937601 |
| Point mutations in Czech DMD/BMD patients and their phenotypic outcome. | Sedlácková J | Neuromuscular disorders : NMD | 2009 | PMID: 19783145 |
| Rapid and cost effective detection of small mutations in the DMD gene by high resolution melting curve analysis. | Almomani R | Neuromuscular disorders : NMD | 2009 | PMID: 19409785 |
| Novel mutations of dystrophin gene in DMD patients detected by rapid scanning in biplex exons DHPLC analysis. | Muscarella LA | Biomolecular engineering | 2007 | PMID: 17145200 |
| Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. | Aartsma-Rus A | Muscle & nerve | 2006 | PMID: 16770791 |
| Point mutations in the dystrophin gene: evidence for frequent use of cryptic splice sites as a result of splicing defects. | Tuffery-Giraud S | Human mutation | 1999 | PMID: 10533061 |
| Characterization of two nonsense mutations in the human dystrophin gene. | Fajkusová L | Journal of neurogenetics | 1998 | PMID: 10320864 |
| The identification of point mutations in Duchenne muscular dystrophy patients by using reverse-transcription PCR and the protein truncation test. | Gardner RJ | American journal of human genetics | 1995 | PMID: 7668256 |
| Non-isotopic analysis of single strand conformation polymorphism (SSCP) in the exon 13 region of the human dystrophin gene. | Lenk U | Journal of medical genetics | 1993 | PMID: 8301652 |
| Point mutations at the carboxy terminus of the human dystrophin gene: implications for an association with mental retardation in DMD patients. | Lenk U | Human molecular genetics | 1993 | PMID: 8281150 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DMD | - | - | - | - |
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Text-mined citations for rs104894790 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 10, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.