ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.968_971delinsGCT (p.Gln323fs)

dbSNP: rs1555148035
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000601848 SCV000731727 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2017-10-09 criteria provided, single submitter clinical testing The p.Gln323fs variant in PKP2 has not been previously reported in individuals w ith arrhythmogenic right ventricular cardiomyopathy (ARVC) or in large populatio n studies. This variant is predicted to cause a frameshift, which alters the pro tein?s amino acid sequence beginning at position 323 and leads to a premature te rmination codon 29 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function is an established mechan ism of disease for the PKP2 gene. In summary, although additional studies are re quired to fully establish its clinical significance, the p.Gln323fs variant is l ikely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV002528785 SCV003441205 pathogenic Arrhythmogenic right ventricular dysplasia 9 2022-05-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln323Argfs*29) in the PKP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKP2 are known to be pathogenic (PMID: 15489853, 23911551). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with PKP2-related conditions. For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV003532195 SCV004358906 pathogenic Cardiomyopathy 2023-08-31 criteria provided, single submitter clinical testing This variant replaces 4 nucleotides in exon 3 of the PKP2 gene with 3 novel nucleotides, causing a frameshift and premature truncation stop signal. This variant is expected to result in an absent or nonfunctional protein product. 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.
All of Us Research Program, National Institutes of Health RCV000601848 SCV004828673 pathogenic Arrhythmogenic right ventricular cardiomyopathy 2023-09-18 criteria provided, single submitter clinical testing This variant replaces 4 nucleotides in exon 3 of the PKP2 gene with 3 novel nucleotides, causing a frameshift and premature truncation stop signal. This variant is expected to result in an absent or nonfunctional protein product. 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.

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