ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.2200A>G (p.Ile734Val)

gnomAD frequency: 0.00001  dbSNP: rs556563706
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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 RCV001182516 SCV001347982 likely benign Cardiomyopathy 2019-09-30 criteria provided, single submitter clinical testing
Invitae RCV001343382 SCV001537360 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 778 of the PKP2 protein (p.Ile778Val). This variant is present in population databases (rs556563706, gnomAD 0.05%). This missense change has been observed in individual(s) with atrioventricular nodal reentry tachycardia (PMID: 32508047). ClinVar contains an entry for this variant (Variation ID: 922435). 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.
GeneDx RCV002298883 SCV002587995 uncertain significance not provided 2022-04-28 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics RCV002446995 SCV002732507 uncertain significance Cardiovascular phenotype 2020-12-28 criteria provided, single submitter clinical testing The p.I778V variant (also known as c.2332A>G), located in coding exon 12 of the PKP2 gene, results from an A to G substitution at nucleotide position 2332. The isoleucine at codon 778 is replaced by valine, an amino acid with highly similar properties. This variant was detected in an arrhythmia genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases. (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other 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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