NM_004415.3(DSP):c.712dupA (p.Ile238Asnfs) AND Primary dilated cardiomyopathy

Clinical significance:Likely pathogenic (Last evaluated: Jul 17, 2012)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000038084.2

Allele description [Variation Report for NM_004415.3(DSP):c.712dupA (p.Ile238Asnfs)]

NM_004415.3(DSP):c.712dupA (p.Ile238Asnfs)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.3(DSP):c.712dupA (p.Ile238Asnfs)
HGVS:
  • NC_000006.12:g.7562766dupA
  • NG_008803.1:g.26130_26131insA
  • NP_004406.2:p.Ile238Asnfs
  • LRG_423t1:c.712dupA
  • LRG_423:g.26130_26131insA
  • LRG_423p1:p.Ile238Asnfs
  • NC_000006.11:g.7562999dupA
  • NM_004415.2:c.712_713insA
  • c.712_713insA
  • p.Ile238AsnfsX19
Links:
dbSNP: 397516956
NCBI 1000 Genomes Browser:
rs397516956
Molecular consequence:
  • NM_004415.2:c.712_713insA - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Cardiomyopathy, congestive
Identifiers:
MedGen: C0007193

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000061750Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Jul 17, 2012)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma.

Norgett EE, Hatsell SJ, Carvajal-Huerta L, Cabezas JC, Common J, Purkis PE, Whittock N, Leigh IM, Stevens HP, Kelsell DP.

Hum Mol Genet. 2000 Nov 1;9(18):2761-6.

PubMed [citation]
PMID:
11063735

Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos-like syndrome.

Uzumcu A, Norgett EE, Dindar A, Uyguner O, Nisli K, Kayserili H, Sahin SE, Dupont E, Severs NJ, Leigh IM, Yuksel-Apak M, Kelsell DP, Wollnik B.

J Med Genet. 2006 Feb;43(2):e5.

PubMed [citation]
PMID:
16467215
PMCID:
PMC2564645
See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000061750.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (3)

Description

The Ile238fs variant in DSP has not been reported in the literature nor previously identified by our laboratory. This frameshift variant is predicted to alter the protein’s amino acid sequence beginning at position 238 and lead to a premature termination codon 19 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its clinical significance. Please note: Frameshift and nonsense variants in DSP are common in patients with ARVC (http://arvcdatabase.info/), but recent evidence supports that they can also cause DCM (Elliott 2010, Garcia-Pavia 2011).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Sep 27, 2017