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NM_004415.4(DSP):c.3754G>A (p.Glu1252Lys) AND Cardiomyopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 11, 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:
RCV001176898.4

Allele description [Variation Report for NM_004415.4(DSP):c.3754G>A (p.Glu1252Lys)]

NM_004415.4(DSP):c.3754G>A (p.Glu1252Lys)

Gene:
DSP:desmoplakin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p24.3
Genomic location:
Preferred name:
NM_004415.4(DSP):c.3754G>A (p.Glu1252Lys)
HGVS:
  • NC_000006.12:g.7579944G>A
  • NG_008803.1:g.43308G>A
  • NM_001008844.3:c.3582+172G>A
  • NM_001319034.2:c.3754G>A
  • NM_004415.4:c.3754G>AMANE SELECT
  • NP_001305963.1:p.Glu1252Lys
  • NP_004406.2:p.Glu1252Lys
  • LRG_423t1:c.3754G>A
  • LRG_423:g.43308G>A
  • NC_000006.11:g.7580177G>A
  • NM_004415.2:c.3754G>A
  • NM_004415.3:c.3754G>A
Protein change:
E1252K
Links:
dbSNP: rs1262533485
NCBI 1000 Genomes Browser:
rs1262533485
Molecular consequence:
  • NM_001008844.3:c.3582+172G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001319034.2:c.3754G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004415.4:c.3754G>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
SCV001340996Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Oct 11, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Wolff-Parkinson-White syndrome: De novo variants and evidence for mutational burden in genes associated with atrial fibrillation.

Coban-Akdemir ZH, Charng WL, Azamian M, Paine IS, Punetha J, Grochowski CM, Gambin T, Valdes SO, Cannon B, Zapata G, Hernandez PP, Jhangiani S, Doddapaneni H, Hu J, Boricha F, Muzny DM, Boerwinkle E, Yang Y, Gibbs RA, Posey JE, Wehrens XHT, Belmont JW, et al.

Am J Med Genet A. 2020 Jun;182(6):1387-1399. doi: 10.1002/ajmg.a.61571. Epub 2020 Mar 31.

PubMed [citation]
PMID:
32233023
PMCID:
PMC7275694

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001340996.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This missense variant replaces glutamic acid with lysine at codon 1252 of the DSP protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with Wolff-Parkinson-White syndrome (PMID: 32233023). This variant has been identified in 5/250606 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

Last Updated: Jun 2, 2024