ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.805G>A (p.Gly269Arg)

gnomAD frequency: 0.00015  dbSNP: rs757285245
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001187140 SCV001353831 uncertain significance Cardiomyopathy 2023-09-06 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 269 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 been reported in one individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 22019812). This variant has been identified in 10/251000 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 RCV001240364 SCV001413300 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 269 of the PKP2 protein (p.Gly269Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs757285245, ExAC 0.002%). This missense change has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 22019812). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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.
Fulgent Genetics, Fulgent Genetics RCV001240364 SCV002787038 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2021-08-04 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004008672 SCV004846483 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2024-08-06 criteria provided, single submitter clinical testing This missense variant replaces glycine with arginine at codon 269 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 10/251000 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.

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