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NM_001005242.3(PKP2):c.1379-1998C>T AND Arrhythmogenic right ventricular dysplasia 9

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 22, 2024
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:
RCV002514319.4

Allele description [Variation Report for NM_001005242.3(PKP2):c.1379-1998C>T]

NM_001005242.3(PKP2):c.1379-1998C>T

Gene:
PKP2:plakophilin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p11.21
Genomic location:
Preferred name:
NM_001005242.3(PKP2):c.1379-1998C>T
HGVS:
  • NC_000012.12:g.32843203G>A
  • NG_009000.1:g.58644C>T
  • NM_001005242.2:c.1379-1998C>T
  • NM_001005242.3:c.1379-1998C>TMANE SELECT
  • NM_004572.3:c.1489C>T
  • NM_004572.4:c.1489C>T
  • NP_004563.2:p.Arg497Ter
  • LRG_398:g.58644C>T
  • NC_000012.10:g.32887404G>A
  • NC_000012.11:g.32996137G>A
Protein change:
R497*
Links:
dbSNP: rs151212477
NCBI 1000 Genomes Browser:
rs151212477
Molecular consequence:
  • NM_001005242.3:c.1379-1998C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_004572.4:c.1489C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Arrhythmogenic right ventricular dysplasia 9 (ARVD9)
Synonyms:
ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 9; Arrhythmogenic right ventricular cardiomyopathy, type 9; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 9
Identifiers:
MONDO: MONDO:0012180; MedGen: C1836906; OMIM: 609040

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003025843Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 22, 2024)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.

Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L.

Nat Genet. 2004 Nov;36(11):1162-4. Epub 2004 Oct 17. Erratum in: Nat Genet. 2005 Jan;37(1):106.

PubMed [citation]
PMID:
15489853

Recessive arrhythmogenic right ventricular dysplasia due to novel cryptic splice mutation in PKP2.

Awad MM, Dalal D, Tichnell C, James C, Tucker A, Abraham T, Spevak PJ, Calkins H, Judge DP.

Hum Mutat. 2006 Nov;27(11):1157.

PubMed [citation]
PMID:
17041889
PMCID:
PMC2799897
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003025843.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg497*) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 17041889, 23911551). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 78974). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Feb 16, 2025