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NM_001005242.3(PKP2):c.302G>A (p.Arg101His) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 18, 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:
RCV000246062.5

Allele description [Variation Report for NM_001005242.3(PKP2):c.302G>A (p.Arg101His)]

NM_001005242.3(PKP2):c.302G>A (p.Arg101His)

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.302G>A (p.Arg101His)
HGVS:
  • NC_000012.12:g.32878954C>T
  • NG_009000.1:g.22893G>A
  • NM_001005242.3:c.302G>AMANE SELECT
  • NM_004572.4:c.302G>A
  • NP_001005242.2:p.Arg101His
  • NP_004563.2:p.Arg101His
  • NP_004563.2:p.Arg101His
  • LRG_398t1:c.302G>A
  • LRG_398:g.22893G>A
  • LRG_398p1:p.Arg101His
  • NC_000012.11:g.33031888C>T
  • NM_004572.3:c.302G>A
  • c.302G>A
Protein change:
R101H
Links:
dbSNP: rs149542398
NCBI 1000 Genomes Browser:
rs149542398
Molecular consequence:
  • NM_001005242.3:c.302G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004572.4:c.302G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000319173Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)
Uncertain significance
(Apr 18, 2023)
germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot 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

Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing.

Lopes LR, Zekavati A, Syrris P, Hubank M, Giambartolomei C, Dalageorgou C, Jenkins S, McKenna W; Uk10k Consortium., Plagnol V, Elliott PM.

J Med Genet. 2013 Apr;50(4):228-39. doi: 10.1136/jmedgenet-2012-101270. Epub 2013 Feb 8.

PubMed [citation]
PMID:
23396983
PMCID:
PMC3607113
See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000319173.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (11)

Description

The p.R101H variant (also known as c.302G>A), located in coding exon 2 of the PKP2 gene, results from a G to A substitution at nucleotide position 302. The arginine at codon 101 is replaced by histidine, an amino acid with highly similar properties. This variant has been reported in individuals with Brugada syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy, although many also carried variants in other cardiac-related genes (Pugh TJ et al. Genet Med. 2014;16(8):601-8; Lopes LR et al. J Med Genet, 2013 Apr;50:228-39; Allegue C et al. PLoS ONE. 2015;10(7):e0133037). In addition, this variant was reported in an individual with arrhythmogenic right ventricular cardiomyopathy who was also homozygous for a DSG2 pathogenic mutation (Fressart V et al. Europace. 2010;12(6):861-8). This variant has also been reported as a secondary cardiac variant of unknown significance in an exome cohort (Ng D et al. Circ Cardiovasc Genet. 2013;6(4):337-46). This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in one species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

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

Last Updated: Sep 29, 2024