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

Recent activity

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RNA-seq analysis of MCF7 xenografts after treatment with OP-1250 and/or CDK4/6 i...
RNA-seq analysis of MCF7 xenografts after treatment with OP-1250 and/or CDK4/6 inhibitors palbociclib or ribociclib
RNA-seq analysis of MCF7 xenografts after treatment with OP-1250 and/or CDK4/6 inhibitors palbociclib or ribociclib

BioProject
6 op, op op (1)
BioProject
Burkholderia pseudomallei 1026b chromosome 1, complete sequence
Burkholderia pseudomallei 1026b chromosome 1, complete sequence
gi|385657254|gb|CP002833.1|

Nucleotide
2613361[uid] (1)
Taxonomy
PREDICTED: Phycodurus eques pyruvate dehydrogenase complex component X (pdhx), t...
PREDICTED: Phycodurus eques pyruvate dehydrogenase complex component X (pdhx), transcript variant X1, mRNA
gi|2638730227|ref|XM_061677601.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001245117	Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 23, 2018)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001245117

Agnes Ginges Centre for Molecular Cardiology, Centenary Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 23, 2018)

germline

research

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	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'.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 5, 2022

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