VCV002979986.4 - ClinVar

NM_001005242.3(PKP2):c.275T>C (p.Leu92Ser)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance

2 out of 2 submissions contributed to this classification

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.275T>C (p.Leu92Ser)

Variation ID: 2979986 Accession: VCV002979986.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12p11.21 12: 32878981 (GRCh38) [ NCBI UCSC ] 12: 33031915 (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	Feb 29, 2024	Feb 23, 2026	Sep 15, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001005242.3:c.275T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001005242.2:p.Leu92Ser	missense
NM_001407155.1:c.275T>C	NP_001394084.1:p.Leu92Ser	missense
NM_001407156.1:c.275T>C	NP_001394085.1:p.Leu92Ser	missense
NM_001407157.1:c.275T>C	NP_001394086.1:p.Leu92Ser	missense
NM_001407158.1:c.-53T>C		5 prime UTR
NM_001407159.1:c.-53T>C		5 prime UTR
NM_001407160.1:c.-53T>C		5 prime UTR
NM_001407161.1:c.275T>C	NP_001394090.1:p.Leu92Ser	missense
NM_001407162.1:c.-53T>C		5 prime UTR
NM_004572.4:c.275T>C	NP_004563.2:p.Leu92Ser	missense
NC_000012.12:g.32878981A>G
NC_000012.11:g.33031915A>G
NG_009000.1:g.22866T>C
LRG_398:g.22866T>C
LRG_398t1:c.275T>C	LRG_398p1:p.Leu92Ser

... more HGVS ... less HGVS

Protein change

L92S

Other names

Canonical SPDI

NC_000012.12:32878980:A:G

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.

Exome Aggregation Consortium (ExAC) 0.00001

Links

ClinGen: CA036441 dbSNP: rs763639737 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	2356	2416

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	Uncertain significance (1)	criteria provided, single submitter	Sep 23, 2023	RCV003835096.5
Cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Sep 15, 2025	RCV006548941.1

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.
Uncertain significance (Sep 15, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy	Color Diagnostics, LLC DBA Color Health Accession: SCV007447733.1 First in ClinVar: Feb 15, 2026 Last updated: Feb 15, 2026	Comment: show This missense variant replaces leucine with serine at codon 92 of the PKP2 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PKP2-related disorders in the literature. This variant has been identified in 2/251424 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Platform type: NGS

Uncertain significance (Sep 23, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Arrhythmogenic right ventricular dysplasia 9	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004638217.3 First in ClinVar: Feb 28, 2024 Last updated: Feb 23, 2026	Comment: show 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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 present in population databases (rs763639737, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 92 of the PKP2 protein (p.Leu92Ser). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This missense variant replaces leucine with serine at codon 92 of the PKP2 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PKP2-related disorders in the literature. This variant has been identified in 2/251424 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

Comment:

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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 present in population databases (rs763639737, gnomAD 0.002%). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 92 of the PKP2 protein (p.Leu92Ser).

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 rs763639737 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Feb 25, 2026