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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 8, 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:: RCV003159811.2

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]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003866251	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 8, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20400443, 25351510, 29511324, 30790397, 33652588 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003866251

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 8, 2024)

germline

clinical testing

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

Citation Link

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

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 Ambry Genetics, SCV003866251.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The p.V87L variant (also known as c.259G>C), located in coding exon 2 of the PKP2 gene, results from a G to C substitution at nucleotide position 259. The valine at codon 87 is replaced by leucine, an amino acid with highly similar properties. This alteration has been reported in arrhythmogenic right ventricular cardiomyopathy (ARVC) cohorts; however, clinical details were limited and an additional alteration in PKP2 was identified in a case (Fressart V et al. Europace, 2010 Jun;12:861-8; Mates J et al. Eur J Hum Genet, 2018 Jul;26:1014-1025; Hermida A et al. Eur J Heart Fail, 2019 Jun;21:792-800; Vallverdú-Prats M et al. J Pers Med, 2021 Feb;11:[ePub ahead of print]). Additionally, this alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Lopes LR et al. Heart, 2015 Feb;101:294-301). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Sep 29, 2024

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