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NM_001927.4(DES):c.1216C>T (p.Arg406Trp)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
8 (Most recent: Jan 7, 2021)
Last evaluated:
Feb 11, 2020
Accession:
VCV000016826.9
Variation ID:
16826
Description:
single nucleotide variant
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NM_001927.4(DES):c.1216C>T (p.Arg406Trp)

Allele ID
31865
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
2q35
Genomic location
2: 219421532 (GRCh38) GRCh38 UCSC
2: 220286254 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P17661:p.Arg406Trp
NC_000002.11:g.220286254C>T
NC_000002.12:g.219421532C>T
... more HGVS
Protein change
R406W
Other names
p.R406W:CGG>TGG
Canonical SPDI
NC_000002.12:219421531:C:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA257646
UniProtKB: P17661#VAR_042458
OMIM: 125660.0007
dbSNP: rs121913003
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Aug 20, 2018 RCV000018320.36
Pathogenic 3 criteria provided, multiple submitters, no conflicts May 22, 2018 RCV000056781.5
Pathogenic 1 criteria provided, single submitter Feb 11, 2020 RCV000627795.5
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
DES - - GRCh38
GRCh37
569 607

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Dec 01, 2015)
criteria provided, single submitter
Method: research
Myofibrillar myopathy 1
Allele origin: unknown
Center for Genetic Medicine Research,Children's National Medical Center
Accession: SCV000265769.2
Submitted: (Jan 25, 2016)
Evidence details
Publications
PubMed (1)
Pathogenic
(May 22, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000235790.10
Submitted: (Jan 29, 2019)
Evidence details
Comment:
The R406W variant in the DES gene has been published as a de novo variant in multiple patients with cardiac and skeletal myopathy (Dalakas et … (more)
Pathogenic
(Aug 20, 2018)
criteria provided, single submitter
Method: clinical testing
Myofibrillar myopathy 1
(Autosomal dominant inheritance)
Allele origin: de novo
Institute of Human Genetics, Klinikum rechts der Isar
Accession: SCV001149752.1
Submitted: (Jan 21, 2020)
Evidence details
Pathogenic
(Feb 11, 2020)
criteria provided, single submitter
Method: clinical testing
Muscular dystrophy, limb-girdle, type 2R
Myofibrillar myopathy 1
Allele origin: germline
Invitae
Accession: SCV000552187.7
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (6)
Comment:
This sequence change replaces arginine with tryptophan at codon 406 of the DES protein (p.Arg406Trp). The arginine residue is highly conserved and there is a … (more)
Pathogenic
(Apr 28, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000231642.5
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Mar 11, 2015)
criteria provided, single submitter
Method: clinical testing
Myofibrillar myopathy 1
(Autosomal dominant inheritance)
Allele origin: germline
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine
Accession: SCV000271350.2
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (6)
Comment:
The p.Arg406Trp variant in DES is absent from large populations sequenced by the Exome Aggregation Consortium (exac.broadinstitute.org/) but has been reported i n at least … (more)
Pathogenic
(Jun 01, 2000)
no assertion criteria provided
Method: literature only
MYOPATHY, MYOFIBRILLAR, 1
Allele origin: germline
OMIM
Accession: SCV000038599.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (1)
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: not provided
Epithelial Biology; Institute of Medical Biology, Singapore
Accession: SCV000087894.1
Submitted: (Jul 31, 2012)
Evidence details

Functional evidence

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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 this variant

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Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases. Punetha J Journal of neuromuscular diseases 2016 PMID: 27854218
Viral-mediated expression of desmin mutants to create mouse models of myofibrillar myopathy. Joanne P Skeletal muscle 2013 PMID: 23425003
High cardiovascular morbidity and mortality in myofibrillar myopathies due to DES gene mutations: a 10-year longitudinal study. Wahbi K Neuromuscular disorders : NMD 2012 PMID: 22153487
Desmin mutations in the terminal consensus motif prevent synemin-desmin heteropolymer filament assembly. Chourbagi O Experimental cell research 2011 PMID: 21262226
Desmin-related myopathy: clinical, electrophysiological, radiological, neuropathological and genetic studies. Olivé M Journal of the neurological sciences 2004 PMID: 15050448
A series of West European patients with severe cardiac and skeletal myopathy associated with a de novo R406W mutation in desmin. Dagvadorj A Journal of neurology 2004 PMID: 14991347
Sporadic cardiac and skeletal myopathy caused by a de novo desmin mutation. Park KY Clinical genetics 2000 PMID: 10905661
Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. Dalakas MC The New England journal of medicine 2000 PMID: 10717012
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DES - - - -

Text-mined citations for rs121913003...

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These 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 Oct 21, 2021