NM_004572.3(PKP2):c.1688+1G>A AND Arrhythmogenic right ventricular cardiomyopathy

Clinical significance:Likely pathogenic (Last evaluated: Jul 6, 2012)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000038177.2

Allele description [Variation Report for NM_004572.3(PKP2):c.1688+1G>A]

NM_004572.3(PKP2):c.1688+1G>A

Gene:
PKP2:plakophilin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p11.21
Genomic location:
Preferred name:
NM_004572.3(PKP2):c.1688+1G>A
HGVS:
  • NC_000012.12:g.32841027C>T
  • NG_009000.1:g.60820G>A
  • NM_004572.3:c.1688+1G>A
  • LRG_398t1:c.1688+1G>A
  • LRG_398:g.60820G>A
  • NC_000012.11:g.32993961C>T
  • c.1688+1G>A
Links:
dbSNP: 397517003
NCBI 1000 Genomes Browser:
rs397517003
Molecular consequence:
  • NM_004572.3:c.1688+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
1

Condition(s)

Name:
Arrhythmogenic right ventricular cardiomyopathy (ARVD)
Synonyms:
Arrhythmogenic right ventricular dysplasia
Identifiers:
MedGen: C0349788; OMIM: PS107970

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000061844Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Jul 6, 2012)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided51not 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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine, SCV000061844.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providednot providedclinical testing PubMed (2)

Description

The 1688+1G>A variant in PKP2 has been reported in 1 individual with ARVD/C and was absent from 600 Caucasian controls, supporting a pathogenic role (Fressart 2010). This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Furthermore, pathogenic splice variants are common in the PKP2 gene. In summary, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided5not provided1not provided

Last Updated: Sep 27, 2017