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NM_004415.4(DSP):c.8117A>T (p.Lys2706Met) AND Arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 23, 2024
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:
RCV004002439.3

Allele description [Variation Report for NM_004415.4(DSP):c.8117A>T (p.Lys2706Met)]

NM_004415.4(DSP):c.8117A>T (p.Lys2706Met)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.4(DSP):c.8117A>T (p.Lys2706Met)
Other names:
p.Lys2706Met
HGVS:
  • NC_000006.12:g.7585379A>T
  • NG_008803.1:g.48743A>T
  • NM_001008844.3:c.6320A>T
  • NM_001319034.2:c.6788A>T
  • NM_004415.4:c.8117A>TMANE SELECT
  • NP_001008844.1:p.Lys2107Met
  • NP_001305963.1:p.Lys2263Met
  • NP_004406.2:p.Lys2706Met
  • LRG_423t1:c.8117A>T
  • LRG_423:g.48743A>T
  • NC_000006.11:g.7585612A>T
  • NM_004415.2:c.8117A>T
Protein change:
K2107M
Links:
dbSNP: rs537588390
NCBI 1000 Genomes Browser:
rs537588390
Molecular consequence:
  • NM_001008844.3:c.6320A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001319034.2:c.6788A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004415.4:c.8117A>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
18

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004821610All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Sep 23, 2024) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown18not providednot provided143475not providedclinical testing

Citations

PubMed

Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy.

Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM.

Heart. 2015 Feb;101(4):294-301. doi: 10.1136/heartjnl-2014-306387. Epub 2014 Oct 28.

PubMed [citation]
PMID:
25351510
PMCID:
PMC4345808

Lamin A/C-Related Cardiac Disease: Late Onset With a Variable and Mild Phenotype in a Large Cohort of Patients With the Lamin A/C p.(Arg331Gln) Founder Mutation.

Hoorntje ET, Bollen IA, Barge-Schaapveld DQ, van Tienen FH, Te Meerman GJ, Jansweijer JA, van Essen AJ, Volders PG, Constantinescu AA, van den Akker PC, van Spaendonck-Zwarts KY, Oldenburg RA, Marcelis CL, van der Smagt JJ, Hennekam EA, Vink A, Bootsma M, Aten E, Wilde AA, van den Wijngaard A, Broers JL, Jongbloed JD, et al.

Circ Cardiovasc Genet. 2017 Aug;10(4). doi:pii: e001631. 10.1161/CIRCGENETICS.116.001631.

PubMed [citation]
PMID:
28790152
See all PubMed Citations (3)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004821610.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided18not providednot providedclinical testing PubMed (3)

Description

This missense variant replaces lysine with methionine at codon 2706 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 performed for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 25351510) and in two brothers affected with dilated cardiomyopathy who also carried a pathogenic variant in the LMNA gene (PMID: 28790152). This variant has been identified in 10/282828 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
1germlineunknown143475not providednot provided18not providednot providednot provided

Last Updated: Mar 16, 2025