ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1540G>A (p.Val514Ile)

gnomAD frequency: 0.00012  dbSNP: rs376102257
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000245734 SCV000319107 likely benign Cardiovascular phenotype 2022-02-02 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.
GeneDx RCV000521548 SCV000620142 uncertain significance not provided 2020-02-20 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 263765; Landrum et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function
Color Diagnostics, LLC DBA Color Health RCV001183826 SCV001349668 likely benign Cardiomyopathy 2021-03-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001348150 SCV001542438 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 558 of the PKP2 protein (p.Val558Ile). This variant is present in population databases (rs376102257, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. 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: 263765). 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 disruptive. 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.

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