ClinVar Genomic variation as it relates to human health
NM_004006.3(DMD):c.8608C>T (p.Arg2870Ter)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004006.3(DMD):c.8608C>T (p.Arg2870Ter)
Variation ID: 94810 Accession: VCV000094810.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xp21.2 X: 31479043 (GRCh38) [ NCBI UCSC ] X: 31497160 (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 Jun 28, 2015 Feb 28, 2024 Mar 3, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004006.3:c.8608C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003997.2:p.Arg2870Ter nonsense NM_000109.4:c.8584C>T NP_000100.3:p.Arg2862Ter nonsense NM_004009.3:c.8596C>T NP_004000.1:p.Arg2866Ter nonsense NM_004010.3:c.8239C>T NP_004001.1:p.Arg2747Ter nonsense NM_004011.4:c.4585C>T NP_004002.3:p.Arg1529Ter nonsense NM_004012.4:c.4576C>T NP_004003.2:p.Arg1526Ter nonsense NM_004013.3:c.1228C>T NP_004004.2:p.Arg410Ter nonsense NM_004014.3:c.421C>T NP_004005.2:p.Arg141Ter nonsense NM_004020.4:c.1228C>T NP_004011.3:p.Arg410Ter nonsense NM_004021.3:c.1228C>T NP_004012.2:p.Arg410Ter nonsense NM_004022.3:c.1228C>T NP_004013.2:p.Arg410Ter nonsense NM_004023.3:c.1228C>T NP_004014.2:p.Arg410Ter nonsense NC_000023.11:g.31479043G>A NC_000023.10:g.31497160G>A NG_012232.1:g.1865567C>T LRG_199:g.1865567C>T LRG_199t1:c.8608C>T LRG_199p1:p.Arg2870Ter - Protein change
- R2870*, R1526*, R1529*, R410*, R2747*, R2862*, R2866*, R141*
- Other names
- NP_003997.1:p.Arg2870*
- Canonical SPDI
- NC_000023.11:31479042: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
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The frequency of the allele represented by this VCV record.
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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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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. |
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DMD | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9080 | 9369 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 17, 2023 | RCV000080803.14 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jan 30, 2023 | RCV000179204.10 | |
Dystrophin deficiency
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Pathogenic (1) |
no assertion criteria provided
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May 15, 2020 | RCV001831875.1 |
DMD-related disorder
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Pathogenic (1) |
criteria provided, single submitter
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Mar 3, 2023 | RCV004528291.1 |
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
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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
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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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Pathogenic
(Jan 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
(X-linked recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV000255754.2
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2015
Comment:
X-linked recessive inheritance
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Pathogenic
(Dec 16, 2022)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
Affected status: yes
Allele origin:
germline
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Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV002769625.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
PVS1, PM2, PP5
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Pathogenic
(Mar 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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DMD-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004110988.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The DMD c.8608C>T variant is predicted to result in premature protein termination (p.Arg2870*). This variant has been reported in many individuals with Duchenne muscular dystrophy … (more)
The DMD c.8608C>T variant is predicted to result in premature protein termination (p.Arg2870*). This variant has been reported in many individuals with Duchenne muscular dystrophy (reported as "8921C>T; R2905X" in Mendell et al. 2001. PubMed ID: 11524473; Cho et al. 2017. PubMed ID: 27593222; Table S3 in Fan et al. 2021. PubMed ID: 34006472). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in DMD are expected to be pathogenic, and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/94810). This variant is interpreted as pathogenic. (less)
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Pathogenic
(Jan 17, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002022894.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000550335.5
First in ClinVar: Oct 19, 2015 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 94810). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 94810). This premature translational stop signal has been observed in individuals with Duchenne muscular dystrophy (PMID: 11524473, 16834926, 19783145, 20098710, 20485447, 21396098, 23588064). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg2870*) 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). (less)
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Pathogenic
(Dec 14, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000112705.8
First in ClinVar: Jan 23, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 5
Sex: mixed
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Pathogenic
(Nov 20, 2017)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001764249.1
First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021 |
Comment:
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; This … (more)
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; This variant is associated with the following publications: (PMID: 27593222, 26968818, 19783145, 11524473, 25525159, 23588064, 20485447, 17253928, 12632325) (less)
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Pathogenic
(May 31, 2019)
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no assertion criteria provided
Method: research
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Duchenne muscular dystrophy
Affected status: yes
Allele origin:
de novo
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Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital
Accession: SCV001482345.1
First in ClinVar: Mar 07, 2021 Last updated: Mar 07, 2021 |
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Pathogenic
(May 15, 2020)
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no assertion criteria provided
Method: clinical testing
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Becker muscular dystrophy
Cardiomyopathy Duchenne muscular dystrophy Dystrophin deficiency
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002087660.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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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 |
Molecular analysis of the dystrophin gene in 407 Chinese patients with Duchenne/Becker muscular dystrophy by the combination of multiplex ligation-dependent probe amplification and Sanger sequencing. | Chen WJ | Clinica chimica acta; international journal of clinical chemistry | 2013 | PMID: 23588064 |
Clinical and molecular characterization of a cohort of patients with novel nucleotide alterations of the Dystrophin gene detected by direct sequencing. | Magri F | BMC medical genetics | 2011 | PMID: 21396098 |
Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. | Takeshima Y | Journal of human genetics | 2010 | PMID: 20485447 |
Dystrophin gene mutation location and the risk of cognitive impairment in Duchenne muscular dystrophy. | Taylor PJ | PloS one | 2010 | PMID: 20098710 |
Point mutations in Czech DMD/BMD patients and their phenotypic outcome. | Sedlácková J | Neuromuscular disorders : NMD | 2009 | PMID: 19783145 |
[Detection of new mutations in the dystrophin gene by denaturing high-performance liquid chromatography]. | Chen YN | Zhonghua er ke za zhi = Chinese journal of pediatrics | 2007 | PMID: 17880784 |
Simultaneous MLPA-based multiplex point mutation and deletion analysis of the dystrophin gene. | Bunyan DJ | Molecular biotechnology | 2007 | PMID: 17435279 |
A different spectrum of DMD gene mutations in local Chinese patients with Duchenne/Becker muscular dystrophy. | Lo IF | Chinese medical journal | 2006 | PMID: 16834926 |
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 |
Diagnosis of Duchenne dystrophy by enhanced detection of small mutations. | Mendell JR | Neurology | 2001 | PMID: 11524473 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DMD | - | - | - | - |
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Text-mined citations for rs398124074 ...
HelpRecord last updated Jun 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.