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NM_001005242.3(PKP2):c.2229dup (p.Leu744fs) AND Aborted sudden cardiac death

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 23, 2018
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:
RCV001089639.1

Allele description [Variation Report for NM_001005242.3(PKP2):c.2229dup (p.Leu744fs)]

NM_001005242.3(PKP2):c.2229dup (p.Leu744fs)

Gene:
PKP2:plakophilin 2 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
12p11.21
Genomic location:
Preferred name:
NM_001005242.3(PKP2):c.2229dup (p.Leu744fs)
HGVS:
  • NC_000012.12:g.32796238dup
  • NG_009000.1:g.105610dup
  • NM_001005242.3:c.2229dupMANE SELECT
  • NM_004572.4:c.2361dup
  • NP_001005242.2:p.Leu744fs
  • NP_004563.2:p.Leu788fs
  • LRG_398:g.105610dup
  • NC_000012.11:g.32949172dup
  • NM_004572.3:c.2361dupT
Protein change:
L744fs
Links:
dbSNP: rs1956121988
NCBI 1000 Genomes Browser:
rs1956121988
Molecular consequence:
  • NM_001005242.3:c.2229dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004572.4:c.2361dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Aborted sudden cardiac death
Identifiers:
MedGen: C4703449; Human Phenotype Ontology: HP:0031628

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001245117Agnes Ginges Centre for Molecular Cardiology, Centenary Institute
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Jul 23, 2018) 		germlineresearch

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedresearch

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, SCV001245117.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)

Description

PKP2 Leu744Serfs*3 has not been previously reported and is absent from the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified this variant in a proband of south-east Asian descent whom presented with cardiac arrest. The patient was also found to have a second variant (DSC2 p.Arg132Cys). Clinical screening did not uncover any abnormal findings, but it is possible that the patient may have a 'concealed' ARVC phenotype. The proband has no family history disease or sudden death. In summary, the variant is likely to result in a truncated PKP2 gene and loss of function is a known mechanism of disease in PKP2, furthermore the variant is very rare in population databases, therefore we classify PKP2 Leu744Serfs*3 as 'likely pathogenic'.

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

Last Updated: Nov 5, 2022