Submissions for variant NM_001005242.3(PKP2):c.256dup (p.Tyr86fs)

dbSNP: rs794729120

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000183780	SCV000236261	pathogenic	not provided	2023-10-26	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26582918)
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852449	SCV000995141	pathogenic	Arrhythmogenic right ventricular cardiomyopathy	2019-03-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001221489	SCV001393537	pathogenic	Arrhythmogenic right ventricular dysplasia 9	2019-07-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr86Leufs*9) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). This variant has not been reported in the literature in individuals with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 202010).
Color Diagnostics, LLC DBA Color Health	RCV005402876	SCV006064427	pathogenic	Cardiomyopathy	2024-05-22	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 2 of the PKP2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with PKP2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PKP2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.