NM_002667.4(PLN):c.116T>G (p.Leu39Ter) AND Familial hypertrophic cardiomyopathy 18

Clinical significance:Pathogenic (Last evaluated: Jan 1, 2011)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_002667.4(PLN):c.116T>G (p.Leu39Ter)]

NM_002667.4(PLN):c.116T>G (p.Leu39Ter)

CEP85L:centrosomal protein 85 like [Gene - HGNC]
PLN:phospholamban [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_002667.4(PLN):c.116T>G (p.Leu39Ter)
  • NC_000006.12:g.118559037T>G
  • NG_009082.1:g.15759T>G
  • NM_002667.4:c.116T>G
  • NP_002658.1:p.Leu39Ter
  • LRG_390t1:c.116T>G
  • LRG_390:g.15759T>G
  • LRG_390p1:p.Leu39Ter
  • NC_000006.11:g.118880200T>G
  • NM_002667.3:c.116T>G
  • p.Leu39X
Protein change:
L39*; LEU39TER
OMIM: 172405.0002; dbSNP: rs111033560
NCBI 1000 Genomes Browser:
Allele Frequency:
Molecular consequence:
  • NM_002667.4:c.116T>G - nonsense - [Sequence Ontology: SO:0001587]


Familial hypertrophic cardiomyopathy 18 (CMH18)
MedGen: C3151265; OMIM: 613874

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000044001OMIMno assertion criteria providedPathogenic
(Jan 1, 2011)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human.

Haghighi K, Kolokathis F, Pater L, Lynch RA, Asahi M, Gramolini AO, Fan GC, Tsiapras D, Hahn HS, Adamopoulos S, Liggett SB, Dorn GW 2nd, MacLennan DH, Kremastinos DT, Kranias EG.

J Clin Invest. 2003 Mar;111(6):869-76.

PubMed [citation]

Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy.

Chiu C, Tebo M, Ingles J, Yeates L, Arthur JW, Lind JM, Semsarian C.

J Mol Cell Cardiol. 2007 Sep;43(3):337-43. Epub 2007 Jun 30.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000044001.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)


In 2 unrelated families with idiopathic dilated cardiomyopathy (609909), Haghighi et al. (2003) identified a 116T-G transversion in the PLN gene, resulting in a leu39-to-ter (L39X) substitution that truncated the 52-amino acid protein in the highly conserved transmembrane domain II. The 2 homozygous individuals developed dilated cardiomyopathy and heart failure requiring cardiac transplantation at ages 16 and 27 years, respectively; 11 heterozygous individuals exhibited variable clinical findings indicating incomplete penetrance of the cardiomyopathy phenotype: 2 had dilated cardiomyopathy with ejection fractions of 25% or less, 4 had left ventricular hypertrophy with normal left ventricular systolic function, and 5 had normal echocardiograms.

In a 65-year-old Australian woman who was diagnosed with familial hypertrophic cardiomyopathy (CMH18; 613874) at age 61 years, Chiu et al. (2007) identified heterozygosity for the L39X mutation in the PLN gene. Echocardiography revealed asymmetric septal hypertrophy with a maximum wall thickness of 20 mm, normal systolic contractile function, and no evidence of left ventricular dilation. Her mother had also been diagnosed with CMH and had died at age 80 of noncardiac causes.

In a 58-year-old man with CMH18, Landstrom et al. (2011) identified heterozygosity for the L39X mutation in the PLN gene. The mutation segregated with disease in the family and was not found in 300 controls.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2018