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NM_001005242.3(PKP2):c.1063C>T (p.Arg355Ter) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 1, 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:
RCV004020235.1

Allele description [Variation Report for NM_001005242.3(PKP2):c.1063C>T (p.Arg355Ter)]

NM_001005242.3(PKP2):c.1063C>T (p.Arg355Ter)

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.1063C>T (p.Arg355Ter)
Other names:
p.R355*:CGA>TGA
HGVS:
  • NC_000012.12:g.32869034G>A
  • NG_009000.1:g.32813C>T
  • NM_001005242.3:c.1063C>TMANE SELECT
  • NM_004572.4:c.1063C>T
  • NP_001005242.2:p.Arg355Ter
  • NP_001005242.2:p.Arg355Ter
  • NP_004563.2:p.Arg355Ter
  • NP_004563.2:p.Arg355Ter
  • LRG_398t1:c.1063C>T
  • LRG_398:g.32813C>T
  • LRG_398p1:p.Arg355Ter
  • NC_000012.11:g.33021968G>A
  • NM_001005242.2:c.1063C>T
  • NM_004572.3:c.1063C>T
Protein change:
R355*
Links:
dbSNP: rs754912778
NCBI 1000 Genomes Browser:
rs754912778
Molecular consequence:
  • NM_001005242.3:c.1063C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_004572.4:c.1063C>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
SCV005022527Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 1, 2023) 		germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

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

Citations

PubMed

Correlation of ventricular arrhythmias with genotype in arrhythmogenic right ventricular cardiomyopathy.

Bao J, Wang J, Yao Y, Wang Y, Fan X, Sun K, He DS, Marcus FI, Zhang S, Hui R, Song L.

Circ Cardiovasc Genet. 2013 Dec;6(6):552-6. doi: 10.1161/CIRCGENETICS.113.000122. Epub 2013 Oct 14.

PubMed [citation]
PMID:
24125834

Comprehensive analysis of desmosomal gene mutations in Han Chinese patients with arrhythmogenic right ventricular cardiomyopathy.

Zhou X, Chen M, Song H, Wang B, Chen H, Wang J, Wang W, Feng S, Zhang F, Ju W, Li M, Gu K, Cao K, Wang DW, Yang B.

Eur J Med Genet. 2015 Apr;58(4):258-65. doi: 10.1016/j.ejmg.2015.02.009. Epub 2015 Mar 9.

PubMed [citation]
PMID:
25765472
See all PubMed Citations (9)

Details of each submission

From Ambry Genetics, SCV005022527.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

The p.R355* pathogenic mutation (also known as c.1063C>T), located in coding exon 4 of the PKP2 gene, results from a C to T substitution at nucleotide position 1063. This changes the amino acid from an arginine to a stop codon within coding exon 4. This alteration has been reported in association with arrhythmogenic right ventricular cardiomyopathy (ARVC) (Bao J et al. Circ Cardiovasc Genet, 2013 Dec;6:552-6; Zhou X et al. Eur J Med Genet, 2015 Apr;58:258-65; Castro SA et al. HeartRhythm Case Rep, 2016 Nov;2:469-472). This alteration has also been reported in biobank and whole exome sequencing cohorts (Haggerty CM et al. Genet Med, 2017 Nov;19:1245-1252; Xiao H et al. World J Pediatr, 2022 Oct;18:687-694; Bourfiss M et al. Circ Genom Precis Med, 2022 Dec;15:e003704). 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: Sep 29, 2024