NM_004415.4(DSP):c.3195C>G (p.Tyr1065Ter) AND Familial isolated arrhythmogenic right ventricular dysplasia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 9, 2022
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:: RCV002265716.1

Allele description [Variation Report for NM_004415.4(DSP):c.3195C>G (p.Tyr1065Ter)]

NM_004415.4(DSP):c.3195C>G (p.Tyr1065Ter)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.3195C>G (p.Tyr1065Ter)

HGVS:

NC_000006.12:g.7579385C>G
NG_008803.1:g.42749C>G
NM_001008844.3:c.3195C>G
NM_001319034.2:c.3195C>G
NM_004415.4:c.3195C>GMANE SELECT
NP_001008844.1:p.Tyr1065Ter
NP_001305963.1:p.Tyr1065Ter
NP_004406.2:p.Tyr1065Ter
LRG_423t1:c.3195C>G
LRG_423:g.42749C>G
NC_000006.11:g.7579618C>G
NM_004415.2:c.3195C>G
NM_004415.3:c.3195C>G

Protein change:

Y1065*

Links:

dbSNP: rs886039178

NCBI 1000 Genomes Browser:

rs886039178

Molecular consequence:

NM_001008844.3:c.3195C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001319034.2:c.3195C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_004415.4:c.3195C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Familial isolated arrhythmogenic right ventricular dysplasia
Identifiers:: MONDO: MONDO:0016342; MedGen: C4274968; OMIM: PS107970

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
SCV002548323	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (May 9, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27532257, 32372669 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002548323

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(May 9, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

Desmoplakin Cardiomyopathy, a Fibrotic and Inflammatory Form of Cardiomyopathy Distinct From Typical Dilated or Arrhythmogenic Right Ventricular Cardiomyopathy.

Smith ED, Lakdawala NK, Papoutsidakis N, Aubert G, Mazzanti A, McCanta AC, Agarwal PP, Arscott P, Dellefave-Castillo LM, Vorovich EE, Nutakki K, Wilsbacher LD, Priori SG, Jacoby DL, McNally EM, Helms AS.

Circulation. 2020 Jun 9;141(23):1872-1884. doi: 10.1161/CIRCULATIONAHA.119.044934. Epub 2020 May 6.

PubMed [citation]

PMID:: 32372669
PMCID:: PMC7286080

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002548323.1

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

Description

Variant summary: DSP c.3195C>G (p.Tyr1065X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251006 control chromosomes. c.3195C>G has been reported in the literature in individuals affected with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was 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

ClinVar

Relating variation to medicine