NM_002667.5(PLN):c.85C>T (p.Gln29Ter) AND Dilated cardiomyopathy 1P

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 24, 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:: RCV001221395.6

Allele description [Variation Report for NM_002667.5(PLN):c.85C>T (p.Gln29Ter)]

NM_002667.5(PLN):c.85C>T (p.Gln29Ter)

Genes:

CEP85L:centrosomal protein 85 like [Gene - OMIM - HGNC]
PLN:phospholamban [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q22.31

Genomic location:

Preferred name:

NM_002667.5(PLN):c.85C>T (p.Gln29Ter)

HGVS:

NC_000006.12:g.118559006C>T
NG_009082.1:g.15728C>T
NG_021248.1:g.156070G>A
NM_001042475.3:c.1020+6523G>AMANE SELECT
NM_001178035.2:c.1029+6523G>A
NM_002667.5:c.85C>TMANE SELECT
NM_206921.3:c.1020+6523G>A
NP_002658.1:p.Gln29Ter
LRG_390t1:c.85C>T
LRG_390:g.15728C>T
NC_000006.11:g.118880169C>T
NM_002667.3:c.85C>T

Protein change:

Q29*

Links:

dbSNP: rs1779072006

NCBI 1000 Genomes Browser:

rs1779072006

Molecular consequence:

NM_001042475.3:c.1020+6523G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001178035.2:c.1029+6523G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_206921.3:c.1020+6523G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_002667.5:c.85C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Dilated cardiomyopathy 1P (CMD1P)
Identifiers:: MONDO: MONDO:0012362; MedGen: C1835928; Orphanet: 154; OMIM: 609909

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001393436	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 24, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12639993, 17655857, 21167350, 25611685, 26535225, 27532257, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001393436

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 24, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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]

PMID:: 12639993
PMCID:: PMC153772

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]

PMID:: 17655857

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001393436.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Gln29*) in the PLN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acid(s) of the PLN protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PLN-related conditions. ClinVar contains an entry for this variant (Variation ID: 949832). This variant disrupts a region of the PLN protein in which other variant(s) (p.Leu39*) have been determined to be pathogenic (PMID: 12639993, 17655857, 21167350, 25611685, 26535225, 27532257). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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