U.S. flag

An official website of the United States government

NM_002667.5(PLN):c.37AGA[1] (p.Arg14del) AND Primary dilated cardiomyopathy

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Aug 19, 2013
Review status:
criteria provided, conflicting classifications
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:
RCV000037582.9

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
  • LRG_390t1:c.40_42del
  • LRG_390:g.15680AGA[1]
  • NC_000006.11:g.118880120_118880122del
  • NC_000006.11:g.118880121AGA[1]
  • NC_000006.11:g.118880124_118880126delAGA
  • NM_002667.3:c.40_42del
  • 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]
Observations:
3

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Dilated Cardiomyopathy
Identifiers:
EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000061240Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Aug 19, 2013) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV001434217Genetics and Genomics Program, Sidra Medicine
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significanceunknownresearch

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided63not providednot providednot providedclinical testing
not providedunknownyes1not providednot providednot providednot providedresearch

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 (9)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061240.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided6not providednot providedclinical testing PubMed (8)

Description

The p.Arg14del variant in PLN has been identified in >50 individuals with DCM an d >10 individuals with ARVC, and was found to segregate with disease in at least >10 affected relatives with DCM (DeWitt 2006, Haghighi 2006, Posch 2009, van de r Zwagg 2012). Multiple functional studies, including mouse models, all support that the Arg14del variant impacts protein function (Haghighi 2006, Ceholski 2012 a, Ceholski 2012b, Haghighi 2012). In summary, the p.Arg14del variant meets our criteria for pathogenicity (http://www.partners.org/personalizedmedicine/LMM) ba sed on segregation and functional evidence.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided6not provided3not provided

From Genetics and Genomics Program, Sidra Medicine, SCV001434217.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not providednot providednot provided

Last Updated: May 19, 2024