NM_001005242.3(PKP2):c.488A>G (p.His163Arg) AND Arrhythmogenic right ventricular dysplasia 9

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 23, 2022
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:: RCV003618575.1

Allele description

NM_001005242.3(PKP2):c.488A>G (p.His163Arg)

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.488A>G (p.His163Arg)

HGVS:

NC_000012.12:g.32878392T>C
NG_009000.1:g.23455A>G
NG_125461.1:g.344T>C
NM_001005242.3:c.488A>GMANE SELECT
NM_001407155.1:c.488A>G
NM_001407156.1:c.488A>G
NM_001407157.1:c.488A>G
NM_001407158.1:c.161A>G
NM_001407159.1:c.161A>G
NM_001407160.1:c.161A>G
NM_001407161.1:c.488A>G
NM_001407162.1:c.161A>G
NM_004572.4:c.488A>G
NP_001005242.2:p.His163Arg
NP_001394084.1:p.His163Arg
NP_001394085.1:p.His163Arg
NP_001394086.1:p.His163Arg
NP_001394087.1:p.His54Arg
NP_001394088.1:p.His54Arg
NP_001394089.1:p.His54Arg
NP_001394090.1:p.His163Arg
NP_001394091.1:p.His54Arg
NP_004563.2:p.His163Arg
NP_004563.2:p.His163Arg
LRG_398t1:c.488A>G
LRG_398:g.23455A>G
LRG_398p1:p.His163Arg
NC_000012.11:g.33031326T>C
NM_004572.3:c.488A>G

Protein change:

H163R

Molecular consequence:

NM_001005242.3:c.488A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407155.1:c.488A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407156.1:c.488A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407157.1:c.488A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407158.1:c.161A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407159.1:c.161A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407160.1:c.161A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407161.1:c.488A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407162.1:c.161A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_004572.4:c.488A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhythmogenic right ventricular dysplasia 9 (ARVD9)
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 9; Arrhythmogenic right ventricular cardiomyopathy, type 9; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 9
Identifiers:: MONDO: MONDO:0012180; MedGen: C1836906; OMIM: 609040

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004488484	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 23, 2022)	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

SCV004488484

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 23, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004488484.1

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with PKP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 163 of the PKP2 protein (p.His163Arg).

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

Last Updated: Feb 28, 2024

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