ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.985A>C (p.Ser329Arg)

gnomAD frequency: 0.00006  dbSNP: rs779173447
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000540161 SCV000638912 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2024-10-12 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 329 of the PKP2 protein (p.Ser329Arg). This variant is present in population databases (rs779173447, gnomAD 0.01%). 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: 464435). 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.
Color Diagnostics, LLC DBA Color Health RCV001805169 SCV002052888 uncertain significance Cardiomyopathy 2023-09-13 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 329 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 cardiovascular disorders in the literature. This variant has been identified in 3/281418 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.
Ambry Genetics RCV002384125 SCV002695764 uncertain significance Cardiovascular phenotype 2024-03-11 criteria provided, single submitter clinical testing The p.S329R variant (also known as c.985A>C), located in coding exon 3 of the PKP2 gene, results from an A to C substitution at nucleotide position 985. The serine at codon 329 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV003999150 SCV004846445 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-10-30 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 329 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 cardiovascular disorders in the literature. This variant has been identified in 3/281418 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.
GeneDx RCV004721424 SCV005328093 uncertain significance not provided 2024-01-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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