NM_004415.4(DSP):c.5851C>T (p.Arg1951Ter) AND Cardiomyopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 22, 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:: RCV001187850.4

Allele description [Variation Report for NM_004415.4(DSP):c.5851C>T (p.Arg1951Ter)]

NM_004415.4(DSP):c.5851C>T (p.Arg1951Ter)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.5851C>T (p.Arg1951Ter)

HGVS:

NC_000006.12:g.7583113C>T
NG_008803.1:g.46477C>T
NM_001008844.3:c.4054C>T
NM_001319034.2:c.4522C>T
NM_004415.4:c.5851C>TMANE SELECT
NP_001008844.1:p.Arg1352Ter
NP_001305963.1:p.Arg1508Ter
NP_004406.2:p.Arg1951Ter
LRG_423t1:c.5851C>T
LRG_423:g.46477C>T
NC_000006.11:g.7583346C>T
NM_004415.2:c.5851C>T

Protein change:

R1352*

Links:

dbSNP: rs869025395

NCBI 1000 Genomes Browser:

rs869025395

Molecular consequence:

NM_001008844.3:c.4054C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001319034.2:c.4522C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004415.4:c.5851C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Mus musculus S-AKAP84 mRNA, complete cds
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gi|2072304|gb|U95145.1|MMU95145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001354743	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 22, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 12101406, 12802069, 21756917, 26656175, 26899768, 34368507, 35474678, 36768812, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001354743

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 22, 2023)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure.

Choi HJ, Park-Snyder S, Pascoe LT, Green KJ, Weis WI.

Nat Struct Biol. 2002 Aug;9(8):612-20.

PubMed [citation]

PMID:: 12101406

Interaction of the bullous pemphigoid antigen 1 (BP230) and desmoplakin with intermediate filaments is mediated by distinct sequences within their COOH terminus.

Fontao L, Favre B, Riou S, Geerts D, Jaunin F, Saurat JH, Green KJ, Sonnenberg A, Borradori L.

Mol Biol Cell. 2003 May;14(5):1978-92. Epub 2003 Jan 26.

PubMed [citation]

PMID:: 12802069
PMCID:: PMC165091

See all PubMed Citations (9)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001354743.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This variant changes 1 nucleotide in exon 24 of the DSP gene, creating a premature translation stop signal in the last exon. Although functional studies have not been reported, this variant is predicted to escape nonsense-mediated decay and be expressed as a truncated protein with disruption to the plakin repeat domains and downstream C-terminal sequence that have been reported to be essential for interaction with intermediate filaments (PMID: 12101406, 12802069, 21756917). This variant has been reported in 6 unrelated individuals affected with arrhythmogenic cardiomyopathy (PMID: 35474678, 36768812, Delpon 2016, Burns 2019, dissertation, The University of Sydney), in 1 individual affected with familial dilated cardiomyopathy (PMID: 26899768), hypertrophic cardiomyopathy (PMID: 26656175), and acute myocarditis (PMID: 34368507). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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