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NM_002667.5(PLN):c.37AGA[1] (p.Arg14del) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 6, 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:
RCV000244830.4

Allele description [Variation Report for NM_002667.5(PLN):c.37AGA[1] (p.Arg14del)]

NM_002667.5(PLN):c.37AGA[1] (p.Arg14del)

Genes:
CEP85L:centrosomal protein 85 like [Gene - OMIM - HGNC]
PLN:phospholamban [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
6q22.31
Genomic location:
Preferred name:
NM_002667.5(PLN):c.37AGA[1] (p.Arg14del)
HGVS:
  • NC_000006.11:g.118880120_118880122del
  • NC_000006.12:g.118558958AGA[1]
  • NG_009082.1:g.15680AGA[1]
  • NG_021248.1:g.156114CTT[1]
  • NM_001042475.3:c.1020+6570_1020+6572delMANE SELECT
  • NM_001178035.2:c.1029+6570_1029+6572del
  • NM_002667.5:c.36_38delAAG
  • NM_002667.5:c.37AGA[1]MANE SELECT
  • NM_206921.3:c.1020+6570_1020+6572del
  • NP_002658.1:p.Arg14del
  • NP_002658.1:p.Arg14del
  • LRG_390t1:c.37_39AGA[1]
  • LRG_390:g.15680AGA[1]
  • LRG_390p1:p.Arg14del
  • NC_000006.11:g.118880120_118880122del
  • NC_000006.11:g.118880121AGA[1]
  • NC_000006.11:g.118880124_118880126delAGA
  • NC_000006.12:g.118558961_118558963del
  • NM_002667.3:c.37_39AGA[1]
  • NM_002667.3:c.40_42del
  • NM_002667.3:c.40_42delAGA
  • NM_002667.3:c.40_42delAGA
  • NM_002667.4:c.36_38del
  • NM_002667.4:c.40_42del
  • NM_002667.4:c.40_42delAGA
  • NM_002667.5:c.36_38delAAGMANE SELECT
  • NM_002667.5:c.40_42delMANE SELECT
  • c.40_42delAGA
  • p.R14del
Protein change:
R14del
Links:
OMIM: 172405.0003; dbSNP: rs397516784
NCBI 1000 Genomes Browser:
rs397516784
Molecular consequence:
  • NM_002667.5:c.37AGA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001042475.3:c.1020+6570_1020+6572del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001178035.2:c.1029+6570_1029+6572del - intron variant - [Sequence Ontology: SO:0001627]
  • NM_206921.3:c.1020+6570_1020+6572del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000318486Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Apr 6, 2022) 		germlineclinical testing

PubMed (23)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy.

Haghighi K, Kolokathis F, Gramolini AO, Waggoner JR, Pater L, Lynch RA, Fan GC, Tsiapras D, Parekh RR, Dorn GW 2nd, MacLennan DH, Kremastinos DT, Kranias EG.

Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1388-93. Epub 2006 Jan 23.

PubMed [citation]
PMID:
16432188
PMCID:
PMC1360586

Phospholamban R14 deletion results in late-onset, mild, hereditary dilated cardiomyopathy.

DeWitt MM, MacLeod HM, Soliven B, McNally EM.

J Am Coll Cardiol. 2006 Oct 3;48(7):1396-8. Epub 2006 Sep 12.

PubMed [citation]
PMID:
17010801
See all PubMed Citations (23)

Details of each submission

From Ambry Genetics, SCV000318486.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (23)

Description

The c.40_42delAGA pathogenic mutation (also known as p.R14del) is located in coding exon 1 of the PLN gene. This pathogenic mutation results from an in-frame AGA deletion at nucleotide positions 40 to 42. This results in the in-frame deletion of an arginine at codon 14. This mutation has been identified in multiple individuals with arrhythmogenic right ventricular cardiomyopathy (ARVC) or dilated cardiomyopathy (DCM), and it has shown strong segregation with cardiomyopathy in a number of unrelated extended pedigrees (DeWitt M et al. J Am Coll Cardiol. 2006;48(7):1396-8; Haghighi K et al. Proc Natl Acad Sci. U.S.A. 2006;103(5):1388-93; Posch M et al. Heart Rhythm. 2009;6(4):480-6; van der Zwaag PA et al. Eur J Heart Fail. 2012;14(11):1199-207; Groeneweg J et al. Am J Cardiol. 2013;112(8):1197-206). Haploytpe analysis has indicated that this variant is a Dutch founder mutation (van der Zwaag PA et al. 2013. Neth Heart J. 2013;21(6):286-93). Functional assays have demonstrated that this alteration disrupts protein function and leads to dominant negative effects (Haghighi K et al. Proc Natl Acad Sci. U.S.A. 2006;103(5):1388-93; Haghighi K et al. J Mol Cell Cardiol. 2012;52(3):773-82; Ceholski D et al. J Biol Chem. 2012;287(32):26596-605; Ceholski DK et al. J Biol Chem. 2012;287(20):16521-9). In addition, a study has found that PLN gene editing can rescue the abnormalities observed in human cardiomyocytes derived from an affected individual heterozygous for this alteration (Karakikes I et al. Nat Commun. 2015;6:6955). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Oct 20, 2024