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NM_004415.4(DSP):c.4198C>T (p.Arg1400Ter) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 26, 2023
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:
RCV002326982.3

Allele description [Variation Report for NM_004415.4(DSP):c.4198C>T (p.Arg1400Ter)]

NM_004415.4(DSP):c.4198C>T (p.Arg1400Ter)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.4(DSP):c.4198C>T (p.Arg1400Ter)
Other names:
p.R1400*:CGA>TGA; p.R1400*
HGVS:
  • NC_000006.12:g.7580388C>T
  • NG_008803.1:g.43752C>T
  • NM_001008844.3:c.3582+616C>T
  • NM_001319034.2:c.4050+148C>T
  • NM_004415.4:c.4198C>TMANE SELECT
  • NP_004406.2:p.Arg1400Ter
  • LRG_423t1:c.4198C>T
  • LRG_423:g.43752C>T
  • NC_000006.11:g.7580621C>T
  • NM_001008844.1:c.3582+616C>T
  • NM_004415.2:c.4198C>T
  • NM_004415.3:c.4198C>T
Protein change:
R1400*
Links:
dbSNP: rs770873593
NCBI 1000 Genomes Browser:
rs770873593
Molecular consequence:
  • NM_001008844.3:c.3582+616C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001319034.2:c.4050+148C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_004415.4:c.4198C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002626653Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 26, 2023) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Correlation of ventricular arrhythmias with genotype in arrhythmogenic right ventricular cardiomyopathy.

Bao J, Wang J, Yao Y, Wang Y, Fan X, Sun K, He DS, Marcus FI, Zhang S, Hui R, Song L.

Circ Cardiovasc Genet. 2013 Dec;6(6):552-6. doi: 10.1161/CIRCGENETICS.113.000122. Epub 2013 Oct 14.

PubMed [citation]
PMID:
24125834

Early-onset heart failure, alopecia, and cutaneous abnormalities associated with a novel compound heterozygous mutation in desmoplakin.

Antonov NK, Kingsbery MY, Rohena LO, Lee TM, Christiano A, Garzon MC, Lauren CT.

Pediatr Dermatol. 2015 Jan-Feb;32(1):102-8. doi: 10.1111/pde.12484. Epub 2014 Dec 16.

PubMed [citation]
PMID:
25516398
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002626653.3

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

Description

The p.R1400* pathogenic mutation (also known as c.4198C>T), located in coding exon 23 of the DSP gene, results from a C to T substitution at nucleotide position 4198. This changes the amino acid from an arginine to a stop codon within coding exon 23. This mutation has been detected once in an arrhythmogenic right ventricular cardiomyopathy (ARVC) cohort as well as in a three year old male with left-sided heart failure, cutaneous abnormalities, and palmoplantar keratoderma (PPK) who also carried DSP R2284* (Bao J et al. Circ Cardiovasc Genet, 2013 Dec;6:552-6; Antonov NK et al. Pediatr Dermatol Dec;32:102-8). In addition to the clinical data presented in the literature, alterations in DSP that result in haploinsufficiency or protein truncation have been reported in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated cardiomyopathy (DCM) (Fressart V et al. Europace. 2010;12(6):861-8; Elliott P et al. Circ Cardiovasc Genet. 2010;3(4):314-22; Quarta G et al. Circulation. 2011;123(23):2701-9; Garcia-Pavia P et al. Heart. 2011;97(21):1744-52; Rasmussen TB et al. Clin Genet. 2013;84(1):20-30; Pugh TJ et al. Genet Med. 2014;16(8):601-8). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 29, 2024