ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2399C>G (p.Ser800Cys)

gnomAD frequency: 0.00001  dbSNP: rs794728090
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
GeneDx RCV000505715 SCV000233509 uncertain significance not provided 2020-08-05 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Color Diagnostics, LLC DBA Color Health RCV001187621 SCV001354472 uncertain significance Cardiomyopathy 2023-11-09 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 800 of the DSG2 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 reported for this variant. This variant has been reported in one individual affected with arrhythmogenic right ventricular cardiomyopathy who also carried a pathogenic variant in the DSP gene that could explain the observed phenotype (PMID: 28588093). This variant has not been identified 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 RCV001373748 SCV001570480 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-09-29 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 199816). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 800 of the DSG2 protein (p.Ser800Cys).
Ambry Genetics RCV002453644 SCV002738500 uncertain significance Cardiovascular phenotype 2021-11-04 criteria provided, single submitter clinical testing The p.S800C variant (also known as c.2399C>G), located in coding exon 15 of the DSG2 gene, results from a C to G substitution at nucleotide position 2399. The serine at codon 800 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is well 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.