ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1379-2025G>A

gnomAD frequency: 0.00023  dbSNP: rs537458442
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000214067 SCV000272305 uncertain significance not specified 2015-06-05 criteria provided, single submitter clinical testing The p.Gly488Ser variant in PKP2 has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.1% (7/7726) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs537458442). Computational prediction tools and conservation analysis are limited or unavailable for this variant. In summary, the clinical significance of the p.Gly488Ser variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000701715 SCV000830528 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 488 of the PKP2 protein (p.Gly488Ser). This variant is present in population databases (rs537458442, gnomAD 0.07%). 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: 229142). 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 RCV002390584 SCV002697181 likely benign Cardiovascular phenotype 2023-03-28 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000214067 SCV002819626 uncertain significance not specified 2022-12-17 criteria provided, single submitter clinical testing

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