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NM_004415.4(DSP):c.4198C>T (p.Arg1400Ter) AND Arrhythmogenic right ventricular dysplasia 8

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Jan 17, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001336684.2

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]
Observations:
1

Condition(s)

Name:
Arrhythmogenic right ventricular dysplasia 8 (ARVD8)
Synonyms:
ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 8; Arrhythmogenic right ventricular cardiomyopathy, type 8; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 8
Identifiers:
MONDO: MONDO:0011831; MedGen: C1843896; OMIM: 607450

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001530135Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Feb 26, 2018) 		unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004046448New York Genome Center
criteria provided, single submitter

(NYGC Assertion Criteria 2020)		Pathogenic
(Jan 17, 2023) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

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
See all PubMed Citations (4)

Details of each submission

From Baylor Genetics, SCV001530135.1

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

Description

This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

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

From New York Genome Center, SCV004046448.1

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

Description

The c.4198C>T variant identified in this individual has previously been reported in at least two individuals with arrhythmogenic right ventricular cardiomyopathy [PMID: 24125834, 29178656], in an individual with dilated cardiomyopathy [PMID: 33996946], and in a 3-year-old boy affected with severe heart failure and cutaneous abnormalities in compound heterozygosity with p.(Arg2284Ter) [PMID: 25516398]. The c.4198C>T variant has been deposited in ClinVar [ClinVar ID: 199884] as Pathogenic (8 entries) and Likely Pathogenic (1 entry). The c.4198C>T variant is observed in 4 alleles (0.0006% minor allele frequency with 0homozygotes) in population databases (gnomAD v2.1.1 and v3.1.2, TOPMed Freeze 8), suggesting it is not a common benign variant in the populations represented in those databases. The c.4198C>T variant is located in exon 23 of this 24-exon gene, predicted to incorporate a premature termination codon (p.(Arg1400Ter)), and is expected to result in loss-of-function via nonsense-mediated decay. Based on available evidence this c.4198C>T p.(Arg1400Ter) variant identified in DSP is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024