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NM_004415.4(DSP):c.7622G>A (p.Arg2541Lys) AND Cardiomyopathy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Mar 10, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001177077.6

Allele description [Variation Report for NM_004415.4(DSP):c.7622G>A (p.Arg2541Lys)]

NM_004415.4(DSP):c.7622G>A (p.Arg2541Lys)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.4(DSP):c.7622G>A (p.Arg2541Lys)
HGVS:
  • NC_000006.12:g.7584884G>A
  • NG_008803.1:g.48248G>A
  • NM_001008844.3:c.5825G>A
  • NM_001319034.2:c.6293G>A
  • NM_004415.4:c.7622G>AMANE SELECT
  • NP_001008844.1:p.Arg1942Lys
  • NP_001305963.1:p.Arg2098Lys
  • NP_004406.2:p.Arg2541Lys
  • LRG_423t1:c.7622G>A
  • LRG_423:g.48248G>A
  • NC_000006.11:g.7585117G>A
  • NM_004415.2:c.7622G>A
Protein change:
R1942K
Links:
dbSNP: rs142078450
NCBI 1000 Genomes Browser:
rs142078450
Molecular consequence:
  • NM_001008844.3:c.5825G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001319034.2:c.6293G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004415.4:c.7622G>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001341207Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 10, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002043304CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Oct 3, 2019) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Multiple mutations in desmosomal proteins encoding genes in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Bauce B, Nava A, Beffagna G, Basso C, Lorenzon A, Smaniotto G, De Bortoli M, Rigato I, Mazzotti E, Steriotis A, Marra MP, Towbin JA, Thiene G, Danieli GA, Rampazzo A.

Heart Rhythm. 2010 Jan;7(1):22-9. doi: 10.1016/j.hrthm.2009.09.070. Epub 2009 Oct 12.

PubMed [citation]
PMID:
20129281

Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations.

Bauce B, Rampazzo A, Basso C, Mazzotti E, Rigato I, Steriotis A, Beffagna G, Lorenzon A, De Bortoli M, Pilichou K, Marra MP, Corbetti F, Daliento L, Iliceto S, Corrado D, Thiene G, Nava A.

Heart Rhythm. 2011 Nov;8(11):1686-95. doi: 10.1016/j.hrthm.2011.06.026. Epub 2011 Jun 30.

PubMed [citation]
PMID:
21723241
PMCID:
PMC3205183
See all PubMed Citations (4)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001341207.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This missense variant replaces arginine with lysine at codon 2541 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 multiple individuals with arrhythmogenic right ventricular cardiomyopathy (PMID: 21723241, 24070718). However, this variant did not segregate with disease in multiple individuals from one family (PMID: 20129281). This variant has been identified in 5/282902 chromosomes 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.

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

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV002043304.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024