ClinVar Genomic variation as it relates to human health
NM_004006.3(DMD):c.10171C>T (p.Arg3391Ter)
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.10171C>T (p.Arg3391Ter)
Variation ID: 94428 Accession: VCV000094428.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xp21.2 X: 31178721 (GRCh38) [ NCBI UCSC ] X: 31196838 (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 Feb 4, 2024 Mar 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004006.3:c.10171C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003997.2:p.Arg3391Ter nonsense NM_000109.4:c.10147C>T NP_000100.3:p.Arg3383Ter nonsense NM_004009.3:c.10159C>T NP_004000.1:p.Arg3387Ter nonsense NM_004010.3:c.9802C>T NP_004001.1:p.Arg3268Ter nonsense NM_004011.4:c.6148C>T NP_004002.3:p.Arg2050Ter nonsense NM_004012.4:c.6139C>T NP_004003.2:p.Arg2047Ter nonsense NM_004013.3:c.2791C>T NP_004004.2:p.Arg931Ter nonsense NM_004014.3:c.1984C>T NP_004005.2:p.Arg662Ter nonsense NM_004015.3:c.967C>T NP_004006.1:p.Arg323Ter nonsense NM_004016.3:c.967C>T NP_004007.1:p.Arg323Ter nonsense NM_004017.3:c.967C>T NP_004008.1:p.Arg323Ter nonsense NM_004018.3:c.967C>T NP_004009.1:p.Arg323Ter nonsense NM_004019.3:c.967C>T NP_004010.1:p.Arg323Ter nonsense NM_004020.4:c.2791C>T NP_004011.3:p.Arg931Ter nonsense NM_004021.3:c.2791C>T NP_004012.2:p.Arg931Ter nonsense NM_004022.3:c.2791C>T NP_004013.2:p.Arg931Ter nonsense NM_004023.3:c.2791C>T NP_004014.2:p.Arg931Ter nonsense NC_000023.11:g.31178721G>A NC_000023.10:g.31196838G>A NG_012232.1:g.2165889C>T LRG_199:g.2165889C>T LRG_199t1:c.10171C>T LRG_199p1:p.Arg3391Ter - Protein change
- R3391*, R2047*, R2050*, R662*, R3387*, R323*, R3268*, R3383*, R931*
- Other names
- NP_003997.1:p.Arg3391*
- p.R3391*:CGA>TGA
- Canonical SPDI
- NC_000023.11:31178720: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
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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
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. |
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DMD | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9327 | 9620 |
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 (4) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2023 | RCV000180030.13 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Oct 24, 2022 | RCV000183403.13 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000763209.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 10, 2021 | RCV001814051.1 |
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
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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
(Jul 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Abnormality of the musculature
Affected status: yes
Allele origin:
germline
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Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV001755518.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
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Pathogenic
(May 13, 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: SCV000255694.2
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2015
Comment:
X-linked recessive inheritance
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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Becker muscular dystrophy
Dilated cardiomyopathy 3B Duchenne muscular dystrophy
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000893831.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(Feb 21, 2020)
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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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000625823.5
First in ClinVar: Dec 26, 2017 Last updated: May 10, 2021 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg3391*) 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.Arg3391*) in the DMD gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in multiple individuals affected with Duchenne muscular dystrophy (PMID: 8840119, 21515508, 25007885, 19074751, 25612904 20485447, 9544849, 27593222). ClinVar contains an entry for this variant (Variation ID: 94428). Loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
Affected status: yes
Allele origin:
unknown
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3billion
Accession: SCV004013865.1
First in ClinVar: Jul 22, 2023 Last updated: Jul 22, 2023 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. This stop-gained (nonsense) variant is predicted to result in a loss or disruption of normal … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. This stop-gained (nonsense) variant is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000094428/PMID: 8840119). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Muscle weakness (present) , Muscular dystrophy (present)
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Pathogenic
(Mar 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Duchenne muscular dystrophy
(X-linked recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004176684.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
The stop gained c.10171C>T (p.Arg3391Ter) variant in DMD gene has been reported in hemizygous state in individuals affected with Duchenne muscular dystrophy (Mah JK, et … (more)
The stop gained c.10171C>T (p.Arg3391Ter) variant in DMD gene has been reported in hemizygous state in individuals affected with Duchenne muscular dystrophy (Mah JK, et al. 2011; Tuffery-Giraud et al. 2009). The p.Arg3391Ter variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submitters). The nucleotide change c.10171C>T in DMD is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss-of-function variants in DMD are known to be pathogenic (Santos R et al. 2014). For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Abnormality of the musculoskeletal system (present)
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Pathogenic
(Oct 24, 2022)
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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: SCV002022872.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Sep 16, 2016)
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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: SCV000112315.8
First in ClinVar: Jan 23, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 4
Sex: mixed
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Pathogenic
(Mar 12, 2021)
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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: SCV000235858.10
First in ClinVar: Jul 05, 2015 Last updated: Apr 17, 2019 |
Comment:
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; Not … (more)
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; Not observed in large population cohorts (Lek et al., 2016); 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; Reported in association with dystrophinopathy, most often with Duchenne muscular dystrophy (Moizard et al., 2000; Aartsma-Rus et al., 2006); This variant is associated with the following publications: (PMID: 15351422, 27593222, 26968818, 32962870, 17435279, 24349052, 25525159, 10909857, 8840119, 17041906, 30907348, 32820569, 32528171) (less)
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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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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 |
New variants, challenges and pitfalls in DMD genotyping: implications in diagnosis, prognosis and therapy. | Santos R | Journal of human genetics | 2014 | PMID: 25007885 |
A population-based study of dystrophin mutations in Canada. | Mah JK | The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques | 2011 | PMID: 21515508 |
Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase. | Tuffery-Giraud S | Human mutation | 2009 | PMID: 19367636 |
Mutation analysis in a population-based cohort of boys with Duchenne or Becker muscular dystrophy. | Cunniff C | Journal of child neurology | 2009 | PMID: 19074751 |
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 |
Mutation analysis of the dystrophin gene in Southern French DMD or BMD families: from Southern blot to protein truncation test. | Tuffery S | Human genetics | 1998 | PMID: 9544849 |
Seven novel additional small mutations and a new alternative splicing in the human dystrophin gene detected by heteroduplex analysis and restricted RT-PCR heteroduplex analysis of illegitimate transcripts. | Barbieri AM | European journal of human genetics : EJHG | 1996 | PMID: 8840119 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DMD | - | - | - | - |
Text-mined citations for rs398123832 ...
HelpRecord last updated Sep 29, 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.