ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.928G>A (p.Val310Met)

gnomAD frequency: 0.00017  dbSNP: rs768396351
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183705 SCV000236179 uncertain significance not provided 2024-03-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign in association with a PKP2-related disorder to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21636032)
Labcorp Genetics (formerly Invitae), Labcorp RCV000538808 SCV000638909 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 310 of the PKP2 protein (p.Val310Met). This variant is present in population databases (rs768396351, 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: 201962). 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.
Color Diagnostics, LLC DBA Color Health RCV000771950 SCV000904903 uncertain significance Cardiomyopathy 2023-05-09 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 310 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 performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 24/282426 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.
Ambry Genetics RCV002372125 SCV002686668 likely benign Cardiovascular phenotype 2024-06-20 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.
Fulgent Genetics, Fulgent Genetics RCV000538808 SCV002796960 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2021-07-21 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003996826 SCV004846464 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 310 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 performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 24/282426 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.

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.