ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2079A>C (p.Glu693Asp)

gnomAD frequency: 0.00003  dbSNP: rs375595872
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000691323 SCV000819099 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 693 of the DSG2 protein (p.Glu693Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 570467). 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 RCV001186672 SCV001353212 uncertain significance Cardiomyopathy 2023-04-21 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with aspartic acid at codon 693 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 DSG2-related disorders in the literature. 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.
Ambry Genetics RCV002422497 SCV002726795 uncertain significance Cardiovascular phenotype 2023-03-24 criteria provided, single submitter clinical testing The p.E693D variant (also known as c.2079A>C), located in coding exon 14 of the DSG2 gene, results from an A to C substitution at nucleotide position 2079. The glutamic acid at codon 693 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available 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.

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