NM_001005242.3(PKP2):c.1379-2072C>T AND Arrhythmogenic right ventricular dysplasia 9

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 30, 2023
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:: RCV000477349.14

Allele description [Variation Report for NM_001005242.3(PKP2):c.1379-2072C>T]

NM_001005242.3(PKP2):c.1379-2072C>T

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.1379-2072C>T

HGVS:

NC_000012.12:g.32843277G>A
NG_009000.1:g.58570C>T
NM_001005242.3:c.1379-2072C>TMANE SELECT
NM_004572.4:c.1415C>T
NP_004563.2:p.Pro472Leu
NP_004563.2:p.Pro472Leu
LRG_398t1:c.1415C>T
LRG_398:g.58570C>T
LRG_398p1:p.Pro472Leu
NC_000012.11:g.32996211G>A
NM_004572.3:c.1415C>T
p.Pro472Leu

Protein change:

P472L

Links:

dbSNP: rs758950276

NCBI 1000 Genomes Browser:

rs758950276

Molecular consequence:

NM_001005242.3:c.1379-2072C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_004572.4:c.1415C>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000545230	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 30, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 36178741, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000545230

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 30, 2023)

germline

clinical testing

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

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

Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort: The Use of Genetic Testing in Risk Stratification.

van der Meulen MH, Herkert JC, den Boer SL, du Marchie Sarvaas GJ, Blom NA, Ten Harkel ADJ, Breur HMPJ, Rammeloo LAJ, Tanke RB, Marcelis C, van de Laar IMBH, Verhagen JMA, Lekanne Dit Deprez RH, Barge-Schaapveld DQCM, Baas AF, Sammani A, Christiaans I, van Tintelen JP, Dalinghaus M.

Circ Genom Precis Med. 2022 Oct;15(5):e002981. doi: 10.1161/CIRCGEN.120.002981. Epub 2022 Sep 30.

PubMed [citation]

PMID:: 36178741
PMCID:: PMC9622377

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000545230.6

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

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 472 of the PKP2 protein (p.Pro472Leu). This variant is present in population databases (rs758950276, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 36178741). ClinVar contains an entry for this variant (Variation ID: 406546). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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: Jan 19, 2025

ClinVar

Relating variation to medicine