VCV004279838.1 - ClinVar

NM_001005242.3(PKP2):c.1101dup (p.Ser368fs)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Likely pathogenic

This classification is based on the single submission received

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001005242.3(PKP2):c.1101dup (p.Ser368fs)

Variation ID: 4279838 Accession: VCV004279838.1

Type and length

Duplication, 1 bp

Location

Cytogenetic: 12p11.21 12: 32868995-32868996 (GRCh38) [ NCBI UCSC ] 12: 33021929-33021930 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 18, 2025	Oct 18, 2025	Aug 4, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001005242.3:c.1101dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001005242.2:p.Ser368fs	frameshift
NM_001407155.1:c.1101dup	NP_001394084.1:p.Ser368fs	frameshift
NM_001407156.1:c.1101dup	NP_001394085.1:p.Ser368fs	frameshift
NM_001407157.1:c.1101dup	NP_001394086.1:p.Ser368fs	frameshift
NM_001407158.1:c.774dup	NP_001394087.1:p.Ser259fs	frameshift
NM_001407159.1:c.774dup	NP_001394088.1:p.Ser259fs	frameshift
NM_001407160.1:c.774dup	NP_001394089.1:p.Ser259fs	frameshift
NM_001407161.1:c.1101dup	NP_001394090.1:p.Ser368fs	frameshift
NM_001407162.1:c.774dup	NP_001394091.1:p.Ser259fs	frameshift
NM_004572.4:c.1101dup	NP_004563.2:p.Ser368fs	frameshift
NC_000012.12:g.32868996dup
NC_000012.11:g.33021930dup
NG_009000.1:g.32851dup
LRG_398:g.32851dup
LRG_398t1:c.1101dup	LRG_398p1:p.Ser368Ilefs

... more HGVS ... less HGVS

Protein change

S259fs, S368fs

Other names

Canonical SPDI

NC_000012.12:32868995:T:TT

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PKP2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2357	2417

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Arrhythmogenic right ventricular dysplasia 9	Likely pathogenic (1)	criteria provided, single submitter	Aug 4, 2025	RCV005864161.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (Aug 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Arrhythmogenic right ventricular dysplasia 9	Clinical Genomics Laboratory, Washington University in St. Louis Accession: SCV006555857.1 First in ClinVar: Oct 18, 2025 Last updated: Oct 18, 2025	Comment: show The PKP2 c.1101dup (p.Ser368Ilefs*19) variant, to our knowledge, has not been reported in the medical literature. This variant causes a frameshift by inserting a single nucleotide, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. This variant is absent from the general population (gnomAD v2.1.1), indicating it is not a common variant. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

The PKP2 c.1101dup (p.Ser368Ilefs*19) variant, to our knowledge, has not been reported in the medical literature. This variant causes a frameshift by inserting a single nucleotide, leading to a premature termination codon, which is predicted to lead to nonsense mediated decay. This variant is absent from the general population (gnomAD v2.1.1), indicating it is not a common variant. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely pathogenic.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Oct 18, 2025