ClinVar Miner

Submissions for variant NM_001005242.3(PKP2):c.1945A>G (p.Ser649Gly)

gnomAD frequency: 0.00003  dbSNP: rs375295635
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
Color Diagnostics, LLC DBA Color Health RCV001177657 SCV001341906 uncertain significance Cardiomyopathy 2023-02-02 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 693 of the PKP2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/251386 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.
Invitae RCV001241007 SCV001413996 uncertain significance Arrhythmogenic right ventricular dysplasia 9 2023-12-23 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 693 of the PKP2 protein (p.Ser693Gly). This variant is present in population databases (rs375295635, gnomAD 0.002%). This missense change has been observed in individual(s) with PKP2-related conditions (PMID: 29540472, 32880476). ClinVar contains an entry for this variant (Variation ID: 919450). 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.
AiLife Diagnostics, AiLife Diagnostics RCV002223273 SCV002501057 uncertain significance not provided 2022-01-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002418611 SCV002727741 uncertain significance Cardiovascular phenotype 2022-09-25 criteria provided, single submitter clinical testing The p.S693G variant (also known as c.2077A>G), located in coding exon 10 of the PKP2 gene, results from an A to G substitution at nucleotide position 2077. The serine at codon 693 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a cardiomyopathy cohort; however, clinical details were limited (Hazebroek MR et al. Circ Heart Fail, 2018 03;11:e004682). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.