ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1792G>A (p.Gly598Ser)

gnomAD frequency: 0.00003  dbSNP: rs773666300
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620559 SCV000737806 uncertain significance Cardiovascular phenotype 2016-12-07 criteria provided, single submitter clinical testing The p.G598S variant (also known as c.1792G>A), located in coding exon 12 of the DSG2 gene, results from a G to A substitution at nucleotide position 1792. The glycine at codon 598 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000818736 SCV000959365 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-10-13 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 598 of the DSG2 protein (p.Gly598Ser). This variant is present in population databases (rs773666300, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 519359). 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. 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 RCV001190209 SCV001357651 uncertain significance Cardiomyopathy 2023-10-18 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 598 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 9/280530 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.

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