NM_004415.4(DSP):c.7874_7875del (p.Thr2625fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 30, 2019
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:: RCV000696017.3

Allele description [Variation Report for NM_004415.4(DSP):c.7874_7875del (p.Thr2625fs)]

NM_004415.4(DSP):c.7874_7875del (p.Thr2625fs)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.7874_7875del (p.Thr2625fs)

HGVS:

NC_000006.12:g.7585134CA[1]
NG_008803.1:g.48498CA[1]
NM_001008844.3:c.6077_6078del
NM_001319034.2:c.6545_6546del
NM_004415.4:c.7874_7875delMANE SELECT
NP_001008844.1:p.Thr2026fs
NP_001305963.1:p.Thr2182fs
NP_004406.2:p.Thr2625fs
LRG_423t1:c.7874_7875del
LRG_423:g.48498CA[1]
NC_000006.11:g.7585367CA[1]
NM_004415.2:c.7874_7875del
NM_004415.2:c.7874_7875delCA

Protein change:

T2026fs

Links:

dbSNP: rs1561704475

NCBI 1000 Genomes Browser:

rs1561704475

Molecular consequence:

NM_001008844.3:c.6077_6078del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319034.2:c.6545_6546del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004415.4:c.7874_7875del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000824560	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 30, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27698334, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000824560

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 30, 2019)

germline

clinical testing

PubMed (2)
[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

Novel truncating desmoplakin mutation as a potential cause of sudden cardiac death in a family.

Foss-Nieradko B, Franaszczyk M, Śpiewak M, Oręziak A, Płoski R, Bilińska ZT.

Pol Arch Med Wewn. 2016 Sep 27;126(9):704-707. doi: 10.20452/pamw.3567. Epub 2016 Sep 27. No abstract available.

PubMed [citation]

PMID:: 27698334

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000824560.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change results in a premature translational stop signal in the DSP gene (p.Thr2625Argfs*18). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 247 amino acids of the DSP protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with ventricular arrythmia (PMID: 27698334). ClinVar contains an entry for this variant (Variation ID: 574161). This variant disrupts the C-terminus of the DSP protein. Other variant(s) that disrupt this region (p.Glu2728Glyfs*11 ) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. 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: Sep 29, 2024

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