NM_004415.4(DSP):c.1060_1061del (p.Leu354fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 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:: RCV000537408.7

Allele description [Variation Report for NM_004415.4(DSP):c.1060_1061del (p.Leu354fs)]

NM_004415.4(DSP):c.1060_1061del (p.Leu354fs)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.1060_1061del (p.Leu354fs)

HGVS:

NC_000006.12:g.7567367CT[1]
NG_008803.1:g.30731CT[1]
NM_001008844.3:c.1060_1061del
NM_001319034.2:c.1060_1061del
NM_004415.4:c.1060_1061delMANE SELECT
NP_001008844.1:p.Leu354fs
NP_001305963.1:p.Leu354fs
NP_004406.2:p.Leu354fs
LRG_423t1:c.1060_1061del
LRG_423:g.30731CT[1]
NC_000006.11:g.7567600CT[1]
NC_000006.11:g.7567600_7567601del
NM_004415.2:c.1060_1061del
NM_004415.2:c.1060_1061delCT

Protein change:

L354fs

Links:

dbSNP: rs1249913357

NCBI 1000 Genomes Browser:

rs1249913357

Molecular consequence:

NM_001008844.3:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001319034.2:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004415.4:c.1060_1061del - 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
SCV000639732	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 17, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 31386562, 20716751, 24503780, 25227139, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000639732

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 17, 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

Arrhythmogenic Right Ventricular Cardiomyopathy-Associated Desmosomal Variants Are Rarely De Novo.

van Lint FHM, Murray B, Tichnell C, Zwart R, Amat N, Lekanne Deprez RH, Dittmann S, Stallmeyer B, Calkins H, van der Smagt JJ, van den Wijngaard A, Dooijes D, van der Zwaag PA, Schulze-Bahr E, Judge DP, Jongbloed JDH, van Tintelen JP, James CA.

Circ Genom Precis Med. 2019 Aug;12(8):e002467. doi: 10.1161/CIRCGEN.119.002467. Epub 2019 Aug 6.

PubMed [citation]

PMID:: 31386562

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000639732.6

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 464956). This premature translational stop signal has been observed in individual(s) with DSP-related conditions (PMID: 31386562). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu354Alafs*15) 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).

#	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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