ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1379-2051G>A

gnomAD frequency: 0.00001  dbSNP: rs1408803372
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000770414 SCV000901857 uncertain significance Cardiomyopathy 2017-01-19 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000770414 SCV001350053 uncertain significance Cardiomyopathy 2023-02-02 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tyrosine at codon 479 of the PKP2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). 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 2/272886 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002533961 SCV003261709 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2023-10-22 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 479 of the PKP2 protein (p.Cys479Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PKP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 626802). 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. 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.
All of Us Research Program, National Institutes of Health RCV003999943 SCV004846399 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-09-04 criteria provided, single submitter clinical testing This missense variant replaces cysteine with tyrosine at codon 479 of the PKP2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/272886 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.
Mayo Clinic Laboratories, Mayo Clinic RCV004792436 SCV005408299 uncertain significance not provided 2023-12-12 criteria provided, single submitter clinical testing

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