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NM_004415.4(DSP):c.6478C>T (p.Arg2160Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 24, 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:
RCV001206927.7

Allele description [Variation Report for NM_004415.4(DSP):c.6478C>T (p.Arg2160Ter)]

NM_004415.4(DSP):c.6478C>T (p.Arg2160Ter)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.4(DSP):c.6478C>T (p.Arg2160Ter)
HGVS:
  • NC_000006.12:g.7583740C>T
  • NG_008803.1:g.47104C>T
  • NM_001008844.3:c.4681C>T
  • NM_001319034.2:c.5149C>T
  • NM_004415.4:c.6478C>TMANE SELECT
  • NP_001008844.1:p.Arg1561Ter
  • NP_001305963.1:p.Arg1717Ter
  • NP_004406.2:p.Arg2160Ter
  • LRG_423t1:c.6478C>T
  • LRG_423:g.47104C>T
  • NC_000006.11:g.7583973C>T
  • NM_004415.2:c.6478C>T
Protein change:
R1561*
Links:
dbSNP: rs777573018
NCBI 1000 Genomes Browser:
rs777573018
Molecular consequence:
  • NM_001008844.3:c.4681C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001319034.2:c.5149C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004415.4:c.6478C>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001378261Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 24, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Incremental value of cardiac magnetic resonance imaging in arrhythmic risk stratification of arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers.

te Riele AS, Bhonsale A, James CA, Rastegar N, Murray B, Burt JR, Tichnell C, Madhavan S, Judge DP, Bluemke DA, Zimmerman SL, Kamel IR, Calkins H, Tandri H.

J Am Coll Cardiol. 2013 Nov 5;62(19):1761-9. doi: 10.1016/j.jacc.2012.11.087. Epub 2013 Jun 27.

PubMed [citation]
PMID:
23810894
PMCID:
PMC3971056

Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy.

Dal Ferro M, Stolfo D, Altinier A, Gigli M, Perrieri M, Ramani F, Barbati G, Pivetta A, Brun F, Monserrat L, Giacca M, Mestroni L, Merlo M, Sinagra G.

Heart. 2017 Nov;103(21):1704-1710. doi: 10.1136/heartjnl-2016-311017. Epub 2017 Apr 17.

PubMed [citation]
PMID:
28416588
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001378261.5

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

Description

This premature translational stop signal has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy or dilated cardiomyopathy (PMID: 23810894, 28416588). This sequence change creates a premature translational stop signal (p.Arg2160*) in the DSP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 712 amino acid(s) of the DSP protein. This variant is present in population databases (rs777573018, gnomAD 0.002%). ClinVar contains an entry for this variant (Variation ID: 199902). This variant disrupts a region of the DSP protein in which other variant(s) (p.Glu2728Glyfs*11) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 7, 2024