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NM_001005242.3(PKP2):c.1234C>T (p.Gln412Ter) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 11, 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:
RCV002360879.2

Allele description [Variation Report for NM_001005242.3(PKP2):c.1234C>T (p.Gln412Ter)]

NM_001005242.3(PKP2):c.1234C>T (p.Gln412Ter)

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.1234C>T (p.Gln412Ter)
HGVS:
  • NC_000012.12:g.32850910G>A
  • NG_009000.1:g.50937C>T
  • NM_001005242.3:c.1234C>TMANE SELECT
  • NM_004572.4:c.1234C>T
  • NP_001005242.2:p.Gln412Ter
  • NP_004563.2:p.Gln412Ter
  • NP_004563.2:p.Gln412Ter
  • LRG_398t1:c.1234C>T
  • LRG_398:g.50937C>T
  • LRG_398p1:p.Gln412Ter
  • NC_000012.11:g.33003844G>A
  • NM_004572.3:c.1234C>T
Protein change:
Q412*
Links:
dbSNP: rs1565590309
NCBI 1000 Genomes Browser:
rs1565590309
Molecular consequence:
  • NM_001005242.3:c.1234C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004572.4:c.1234C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002664415Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 11, 2022) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Hermida A, Fressart V, Hidden-Lucet F, Donal E, Probst V, Deharo JC, Chevalier P, Klug D, Mansencal N, Delacretaz E, Cosnay P, Scanu P, Extramiana F, Keller DI, Rouanet S, Charron P, Gandjbakhch E.

Eur J Heart Fail. 2019 Jun;21(6):792-800. doi: 10.1002/ejhf.1423. Epub 2019 Feb 21.

PubMed [citation]
PMID:
30790397

Details of each submission

From Ambry Genetics, SCV002664415.2

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

Description

The p.Q412* pathogenic mutation (also known as c.1234C>T), located in coding exon 5 of the PKP2 gene, results from a C to T substitution at nucleotide position 1234. This changes the amino acid from a glutamine to a stop codon within coding exon 5. This variant has been detected in an individual with arrhythmogenic right ventricular cardiomyopathy (Hermida A et al. Eur J Heart Fail, 2019 06;21:792-800). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: May 1, 2024