NM_004415.4(DSP):c.5984T>C (p.Leu1995Ser) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 28, 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:: RCV001189664.4

Allele description [Variation Report for NM_004415.4(DSP):c.5984T>C (p.Leu1995Ser)]

NM_004415.4(DSP):c.5984T>C (p.Leu1995Ser)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.5984T>C (p.Leu1995Ser)

Other names:

p.L1995S:TTG>TCG

HGVS:

NC_000006.12:g.7583246T>C
NG_008803.1:g.46610T>C
NM_001008844.3:c.4187T>C
NM_001319034.2:c.4655T>C
NM_004415.4:c.5984T>CMANE SELECT
NP_001008844.1:p.Leu1396Ser
NP_001305963.1:p.Leu1552Ser
NP_004406.2:p.Leu1995Ser
LRG_423t1:c.5984T>C
LRG_423:g.46610T>C
NC_000006.11:g.7583479T>C
NM_004415.2:c.5984T>C

Protein change:

L1396S

Links:

dbSNP: rs794728128

NCBI 1000 Genomes Browser:

rs794728128

Molecular consequence:

NM_001008844.3:c.4187T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001319034.2:c.4655T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004415.4:c.5984T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001356995	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29016939, 31737537, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001356995

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 28, 2023)

germline

clinical testing

PubMed (3)
[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

Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases.

Hellenthal N, Gaertner-Rommel A, Klauke B, Paluszkiewicz L, Stuhr M, Kerner T, Farr M, Püschel K, Milting H.

Europace. 2017 Nov 1;19(11):1881-1890. doi: 10.1093/europace/euw247.

PubMed [citation]

PMID:: 29016939

Variant panorama in 1,385 index patients and sensitivity of expanded next-generation sequencing panels in arrhythmogenic disorders.

Marschall C, Moscu-Gregor A, Klein HG.

Cardiovasc Diagn Ther. 2019 Oct;9(Suppl 2):S292-S298. doi: 10.21037/cdt.2019.06.06.

PubMed [citation]

PMID:: 31737537
PMCID:: PMC6837920

See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001356995.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This missense variant replaces leucine with serine at codon 1995 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 31737537) and sudden unexplained death (PMID: 29016939). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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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