U.S. flag

An official website of the United States government

NM_004415.4(DSP):c.3474dup (p.Glu1159fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 31, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000150566.6

Allele description [Variation Report for NM_004415.4(DSP):c.3474dup (p.Glu1159fs)]

NM_004415.4(DSP):c.3474dup (p.Glu1159fs)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.4(DSP):c.3474dup (p.Glu1159fs)
Other names:
p.Glu1159ArgfsX3
HGVS:
  • NC_000006.11:g.7579896_7579897insA
  • NC_000006.12:g.7579664dup
  • NG_008803.1:g.43028dup
  • NM_001008844.3:c.3474dup
  • NM_001319034.2:c.3474dup
  • NM_004415.4:c.3474dupMANE SELECT
  • NP_001008844.1:p.Glu1159fs
  • NP_001305963.1:p.Glu1159fs
  • NP_004406.2:p.Glu1159fs
  • LRG_423t1:c.3474dup
  • LRG_423:g.43028dup
  • NC_000006.11:g.7579896_7579897insA
  • NC_000006.11:g.7579897_7579898insA
  • NC_000006.11:g.7579897dup
  • NM_004415.2:c.3474dupA
Protein change:
E1159fs
Links:
dbSNP: rs727503000
NCBI 1000 Genomes Browser:
rs727503000
Molecular consequence:
  • NM_001008844.3:c.3474dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001319034.2:c.3474dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004415.4:c.3474dup - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
2

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Dilated Cardiomyopathy
Identifiers:
EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644
Name:
Arrhythmogenic right ventricular cardiomyopathy (ARVD)
Synonyms:
Cardiomyopathy, ARVC; Arrhythmogenic right ventricular dysplasia
Identifiers:
MONDO: MONDO:0016587; MedGen: C0349788

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000197818Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Jan 31, 2018) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided132not providednot providednot providedclinical testing

Citations

PubMed

Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy.

Elliott P, O'Mahony C, Syrris P, Evans A, Rivera Sorensen C, Sheppard MN, Carr-White G, Pantazis A, McKenna WJ.

Circ Cardiovasc Genet. 2010 Aug;3(4):314-22. doi: 10.1161/CIRCGENETICS.110.937805.

PubMed [citation]
PMID:
20716751

Desmosomal protein gene mutations in patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation: a clinicopathological study.

Garcia-Pavia P, Syrris P, Salas C, Evans A, Mirelis JG, Cobo-Marcos M, Vilches C, Bornstein B, Segovia J, Alonso-Pulpon L, Elliott PM.

Heart. 2011 Nov;97(21):1744-52. doi: 10.1136/hrt.2011.227967. Epub 2011 Aug 22.

PubMed [citation]
PMID:
21859740
See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000197818.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided13not providednot providedclinical testing PubMed (4)

Description

The p.Glu1159fs variant in DSP has been identified in 2 individuals with ARVC an d 1 individual with DCM. It segregated with disease in 5 affected family members from 2 families (Asimaki 2016, LMM data). It was absent from large population s tudies. This variant is predicted to cause a frameshift, which alters the protei n?s amino acid sequence beginning at position 1159 and leads to a premature term ination codon 2 amino acids downstream. This alteration is then predicted to lea d to a truncated or absent protein. Heterozygous loss of function of the DSP gen e is associated with ARVC and DCM. In summary, this variant meets criteria to be classified as pathogenic for ARVC and DCM in an autosomal dominant manner based upon its loss of function impact, case observations, segregation studies, and a bsence from controls. ACMG/AMP Criteria applied: PVS1; PM2; PP1_Moderate; PS4_Su pporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided13not provided2not provided

Last Updated: Jun 2, 2024