ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.365G>T (p.Arg122Leu)

dbSNP: rs201306582
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001187051 SCV001353710 uncertain significance Cardiomyopathy 2020-10-08 criteria provided, single submitter clinical testing This missense variant replaces arginine with leucine at codon 122 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 1/248096 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.
Invitae RCV001360552 SCV001556477 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 122 of the PKP2 protein (p.Arg122Leu). 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: 925223). 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.
Ambry Genetics RCV002451388 SCV002614001 uncertain significance Cardiovascular phenotype 2021-04-20 criteria provided, single submitter clinical testing The p.R122L variant (also known as c.365G>T), located in coding exon 3 of the PKP2 gene, results from a G to T substitution at nucleotide position 365. The arginine at codon 122 is replaced by leucine, 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.

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