NM_000117.2(EMD):c.454C>T (p.Arg152Cys) AND Emery-Dreifuss muscular dystrophy 1, X-linked

Clinical significance:Uncertain significance (Last evaluated: Aug 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000616618.4

Allele description [Variation Report for NM_000117.2(EMD):c.454C>T (p.Arg152Cys)]

NM_000117.2(EMD):c.454C>T (p.Arg152Cys)

Gene:
EMD:emerin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000117.2(EMD):c.454C>T (p.Arg152Cys)
HGVS:
  • NC_000023.11:g.154380886C>T
  • NG_008677.1:g.11451C>T
  • NM_000117.2:c.454C>T
  • NP_000108.1:p.Arg152Cys
  • LRG_745t1:c.454C>T
  • LRG_745:g.11451C>T
  • LRG_745p1:p.Arg152Cys
  • NC_000023.10:g.153609246C>T
Protein change:
R152C
Links:
dbSNP: rs376456050
NCBI 1000 Genomes Browser:
rs376456050
Molecular consequence:
  • NM_000117.2:c.454C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Emery-Dreifuss muscular dystrophy 1, X-linked (EDMD1)
Synonyms:
EMD-Related Cardiomyopathy; Emery-Dreifuss muscular dystrophy, X-linked; Muscular dystrophy, tardive Emery-Dreifuss type, with contractures; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010680; MedGen: C5243475; Orphanet: 261; Orphanet: 98863; OMIM: 310300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000734765Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensusno assertion criteria providedUncertain significancegermlineclinical testing

SCV000820492Invitaecriteria provided, single submitter
Uncertain significance
(Aug 7, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Targeted sequence capture and GS-FLX Titanium sequencing of 23 hypertrophic and dilated cardiomyopathy genes: implementation into diagnostics.

Mook OR, Haagmans MA, Soucy JF, van de Meerakker JB, Baas F, Jakobs ME, Hofman N, Christiaans I, Lekanne Deprez RH, Mannens MM.

J Med Genet. 2013 Sep;50(9):614-26. doi: 10.1136/jmedgenet-2012-101231. Epub 2013 Jun 19.

PubMed [citation]
PMID:
23785128
PMCID:
PMC3756457

Genetic analysis in 418 index patients with idiopathic dilated cardiomyopathy: overview of 10 years' experience.

van Spaendonck-Zwarts KY, van Rijsingen IA, van den Berg MP, Lekanne Deprez RH, Post JG, van Mil AM, Asselbergs FW, Christiaans I, van Langen IM, Wilde AA, de Boer RA, Jongbloed JD, Pinto YM, van Tintelen JP.

Eur J Heart Fail. 2013 Jun;15(6):628-36. doi: 10.1093/eurjhf/hft013. Epub 2013 Jan 24.

PubMed [citation]
PMID:
23349452
See all PubMed Citations (3)

Details of each submission

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV000734765.1

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

From Invitae, SCV000820492.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine with cysteine at codon 152 of the EMD protein (p.Arg152Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs376456050, ExAC 0.006%). This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 23785128, 23349452). ClinVar contains an entry for this variant (Variation ID: 198043). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C3. The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 5

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

Last Updated: Jun 14, 2021

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