NM_001005242.3(PKP2):c.533dup (p.His179fs) AND Arrhythmogenic right ventricular cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 27, 2017
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:: RCV000600205.4

Allele description [Variation Report for NM_001005242.3(PKP2):c.533dup (p.His179fs)]

NM_001005242.3(PKP2):c.533dup (p.His179fs)

Gene:

PKP2:plakophilin 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

12p11.21

Genomic location:

Preferred name:

NM_001005242.3(PKP2):c.533dup (p.His179fs)

Other names:

p.His179AlafsX37

HGVS:

NC_000012.12:g.32878347dup
NG_009000.1:g.23500dup
NM_001005242.3:c.533dupMANE SELECT
NM_004572.4:c.533dup
NP_001005242.2:p.His179fs
NP_004563.2:p.His179fs
NP_004563.2:p.His179fs
LRG_398t1:c.533dup
LRG_398:g.23500dup
LRG_398p1:p.His179fs
NC_000012.11:g.33031280_33031281insA
NC_000012.11:g.33031281dup
NM_004572.3:c.533dup
NM_004572.3:c.533dup
NM_004572.3:c.533dupT
p.H179AfsX37

Protein change:

H179fs

Links:

dbSNP: rs769220833

NCBI 1000 Genomes Browser:

rs769220833

Molecular consequence:

NM_001005242.3:c.533dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004572.4:c.533dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Arrhythmogenic right ventricular cardiomyopathy (ARVD)
Synonyms:: Cardiomyopathy, ARVC; Arrhythmogenic right ventricular dysplasia
Identifiers:: MONDO: MONDO:0016587; MeSH: D019571; MedGen: C0349788

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000713178	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Jul 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000713178

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Jul 27, 2017)

germline

clinical testing

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	not provided	2	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

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, Mass General Brigham Personalized Medicine, SCV000713178.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

Description

The p.His179fs variant in PKP2 has not been previously reported in the literatur e, but has been reported in ClinVar (Variation ID: 202012). This variant has als o been identified in 1/15302 African chromosomes by the Genome Aggregation Datab ase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs769220833). This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequen ce beginning at position 179 and leads to a premature termination codon 37 amino acids downstream. This alteration is then predicted to lead to a truncated or a bsent protein. Frameshift and other truncating variants in PKP2 are well-reporte d in individuals with ARVC (ARVD/C Genetic Variant Database, http://arvcdatabase .info; Human Gene Mutation Database). In summary, although additional studies ar e required to fully establish its clinical significance, the p.His179fs variant is likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	2	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine