NM_004415.4(DSP):c.1273C>T (p.Arg425Ter) AND Arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 17, 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:: RCV003996331.2

Allele description [Variation Report for NM_004415.4(DSP):c.1273C>T (p.Arg425Ter)]

NM_004415.4(DSP):c.1273C>T (p.Arg425Ter)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.1273C>T (p.Arg425Ter)

HGVS:

NC_000006.12:g.7568443C>T
NG_008803.1:g.31807C>T
NM_001008844.3:c.1273C>T
NM_001319034.2:c.1273C>T
NM_004415.4:c.1273C>TMANE SELECT
NP_001008844.1:p.Arg425Ter
NP_001305963.1:p.Arg425Ter
NP_004406.2:p.Arg425Ter
LRG_423t1:c.1273C>T
LRG_423:g.31807C>T
NC_000006.11:g.7568676C>T
NM_004415.2:c.1273C>T
NM_004415.3:c.1273C>T
c.1273C>T
p.Arg425X
p.R425*

Protein change:

R425*

Links:

dbSNP: rs397516915

NCBI 1000 Genomes Browser:

rs397516915

Molecular consequence:

NM_001008844.3:c.1273C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001319034.2:c.1273C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004415.4:c.1273C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Arrhythmogenic cardiomyopathy with wooly hair and keratoderma
Synonyms:: Palmoplantar keratoderma with left ventricular cardiomyopathy and woolly hair; Epidermolytic palmoplantar keratoderma woolly hair and dilated cardiomyopathy; Dilated cardiomyopathy with woolly hair and keratoderma; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011581; MedGen: C1854063; Orphanet: 65282; OMIM: 605676

Recent activity

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small ubiquitin-related modifier 2 [Heterocephalus glaber]
small ubiquitin-related modifier 2 [Heterocephalus glaber]
gi|1196706339|ref|XP_004838571.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004839389	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 17, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 20716751, 22555271, 24503780, 25227139, 33821670, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004839389

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 17, 2023)

germline

clinical testing

PubMed (6)
[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	1	not provided	not provided	108544	not provided	clinical 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

Pediatric cardiomyopathy: importance of genetic and metabolic evaluation.

Kindel SJ, Miller EM, Gupta R, Cripe LH, Hinton RB, Spicer RL, Towbin JA, Ware SM.

J Card Fail. 2012 May;18(5):396-403. doi: 10.1016/j.cardfail.2012.01.017. Epub 2012 Mar 10.

PubMed [citation]

PMID:: 22555271
PMCID:: PMC3345128

See all PubMed Citations (6)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004839389.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (6)

Description

The c.1273C>T (p.Arg425*) variant in the DSP gene creates a premature translation stop codon. It is predicted to result in a disrupted protein product or absent protein due to nonsense mediated decay. This variant has been observed in patients affected with arrhythmogenic right ventricular cardiomyopathy/ dysplasia (ARVC/D) (PMID: 33821670, 22555271). This variant is rare (1/251268) alleles in the general population database, gnomAD. ClinVar has an entry for this variant (ID:44856). Loss-of-function variants in DSP gene are known to be pathogenic (PMID: 24503780, 20716751, 25227139). Therefore, the c.1273C>T (p.Arg425*) variant in the DSP gene is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Aug 11, 2024

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