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NM_001005242.3(PKP2):c.259G>C (p.Val87Leu) AND Arrhythmogenic right ventricular cardiomyopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 30, 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:
RCV003999146.2

Allele description [Variation Report for NM_001005242.3(PKP2):c.259G>C (p.Val87Leu)]

NM_001005242.3(PKP2):c.259G>C (p.Val87Leu)

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.259G>C (p.Val87Leu)
HGVS:
  • NC_000012.12:g.32878997C>G
  • NG_009000.1:g.22850G>C
  • NM_001005242.3:c.259G>CMANE SELECT
  • NM_004572.4:c.259G>C
  • NP_001005242.2:p.Val87Leu
  • NP_004563.2:p.Val87Leu
  • NP_004563.2:p.Val87Leu
  • LRG_398t1:c.259G>C
  • LRG_398:g.22850G>C
  • LRG_398p1:p.Val87Leu
  • NC_000012.11:g.33031931C>G
  • NM_004572.3:c.259G>C
Protein change:
V87L
Links:
dbSNP: rs750028032
NCBI 1000 Genomes Browser:
rs750028032
Molecular consequence:
  • NM_001005242.3:c.259G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004572.4:c.259G>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
7

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy (ARVD)
Synonyms:
Cardiomyopathy, ARVC; Arrhythmogenic right ventricular dysplasia
Identifiers:
MONDO: MONDO:0016587; MeSH: D019571; MedGen: C0349788

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004844461All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain Significance
(Nov 30, 2023)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown7not providednot provided108544not providedclinical testing

Citations

PubMed

Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice.

Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, Klug D, Dubourg O, Delacretaz E, Cosnay P, Scanu P, Extramiana F, Keller D, Hidden-Lucet F, Simon F, Bessirard V, Roux-Buisson N, Hebert JL, Azarine A, Casset-Senon D, Rouzet F, Lecarpentier Y, et al.

Europace. 2010 Jun;12(6):861-8. doi: 10.1093/europace/euq104. Epub 2010 Apr 16.

PubMed [citation]
PMID:
20400443

Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy.

Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM.

Heart. 2015 Feb;101(4):294-301. doi: 10.1136/heartjnl-2014-306387. Epub 2014 Oct 28.

PubMed [citation]
PMID:
25351510
PMCID:
PMC4345808
See all PubMed Citations (5)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004844461.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided7not providednot providedclinical testing PubMed (5)

Description

This missense variant replaces valine with leucine at codon 87 of the PKP2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in two probands affected with arrhythmogenic cardiomyopathy (PMID: 20400443, 30790397, 33652588). One of the probands and two affected relatives in the family were compound heterozygous for this variant and a pathogenic truncating variant. This variant has also been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 25351510). This variant has been identified in 4/282806 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided7not providednot providednot provided

Last Updated: Sep 29, 2024