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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 1, 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:: RCV001056868.5

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]

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

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001221333	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 1, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22555271, 20716751, 24503780, 25227139, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001221333

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 1, 2023)

germline

clinical testing

PubMed (5)
[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

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

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

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001221333.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This premature translational stop signal has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 22555271). This variant is present in population databases (rs397516915, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg425*) in the DSP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSP are known to be pathogenic (PMID: 20716751, 24503780, 25227139). ClinVar contains an entry for this variant (Variation ID: 44856). For these reasons, this variant has been 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: Aug 11, 2024

ClinVar

Relating variation to medicine