ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1796A>G (p.Lys599Arg)

gnomAD frequency: 0.00003  dbSNP: rs533659697
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000543714 SCV000638875 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2023-10-18 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 643 of the PKP2 protein (p.Lys643Arg). This variant is present in population databases (rs533659697, gnomAD 0.03%). 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: 464416). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV000620310 SCV000737545 likely benign Cardiovascular phenotype 2024-01-04 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757663 SCV000885971 uncertain significance not provided 2017-06-20 criteria provided, single submitter clinical testing The p.Lys643Arg variant (rs533659697) has not been reported in the medical literature and is not listed in gene-specific variant databases. It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in East Asian populations of 0.03% (identified in 6 out of 17,242 chromosomes). The lysine at codon 643 is moderately conserved considering 8 species (Alamut software v2.9), and computational analyses suggest this variant does not have a significant effect on PKP2 protein structure/function (SIFT: tolerated, PolyPhen2: benign, and Mutation Taster: polymorphism). However, based on the available information, the clinical significance of the p.Lys643Arg variant cannot be determined with certainty.
Color Diagnostics, LLC DBA Color Health RCV001184764 SCV001350825 likely benign Cardiomyopathy 2020-07-15 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.