NM_001927.4(DES):c.1216C>T (p.Arg406Trp) AND not provided

Clinical significance:Pathogenic (Last evaluated: May 22, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000056781.5

Allele description [Variation Report for NM_001927.4(DES):c.1216C>T (p.Arg406Trp)]

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

Gene:
DES:desmin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_001927.4(DES):c.1216C>T (p.Arg406Trp)
Other names:
p.R406W:CGG>TGG
HGVS:
  • NC_000002.12:g.219421532C>T
  • NG_008043.1:g.8156C>T
  • NM_001927.4:c.1216C>TMANE SELECT
  • NP_001918.3:p.Arg406Trp
  • LRG_380t1:c.1216C>T
  • LRG_380:g.8156C>T
  • NC_000002.11:g.220286254C>T
  • NM_001927.3:c.1216C>T
  • P17661:p.Arg406Trp
Protein change:
R406W; ARG406TRP
Links:
UniProtKB: P17661#VAR_042458; OMIM: 125660.0007; dbSNP: rs121913003
NCBI 1000 Genomes Browser:
rs121913003
Molecular consequence:
  • NM_001927.4:c.1216C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
3

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000087894Epithelial Biology; Institute of Medical Biology, Singaporeno assertion providednot providednot providednot provided

SCV000231642EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Apr 28, 2016)
germlineclinical testing

Citation Link,

SCV000235790GeneDxcriteria provided, single submitter
Pathogenic
(May 22, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown3not providednot providednot providednot providedclinical testing
not providednot providednot providednot providednot providednot provided1not providedliterature only

Details of each submission

From Epithelial Biology; Institute of Medical Biology, Singapore, SCV000087894.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providednot providednot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot provided1not providednot providednot providednot providednot providednot provided

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000231642.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From GeneDx, SCV000235790.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

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 al., 2000; Park et al., 2000; Dagvadorj et al., 2004). In one study, each of four patients presented with early onset cardiac arrhythmia and conduction block followed by muscle weakness and progressive atrophy in the lower extremities (Dagvadorj et al., 2004). In addition, the R406W variant has been classified as a pathogenic variant by another clinical laboratory in ClinVar (SCV000231642.1; Landrum et al., 2016). The R406W variant, located in the C-terminal part of the desmin core domain, severely affected the ability of desmin to assemble into functional filaments (Park et al., 2000; Chourbagi et al., 2011). The Arginine 406 residue is highly conserved across species, and the R406W variant was not observed in over 300 control chromosomes (Park et al., 2000). Furthermore, the R406W variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, R406W is interpreted to be a pathogenic variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 21, 2021

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