ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2614G>C (p.Glu872Gln) (rs754057911)

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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 RCV000621898 SCV000737775 uncertain significance Cardiovascular phenotype 2016-11-03 criteria provided, single submitter clinical testing The p.E872Q variant (also known as c.2614G>C), located in coding exon 15 of the DSG2 gene, results from a G to C substitution at nucleotide position 2614. The glutamic acid at codon 872 is replaced by glutamine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 5954 samples (11908 alleles) with coverage at this position. Based on data from ExAC, the C allele has an overall frequency of less than 0.01% (1/119976). This amino acid position is 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.
Invitae RCV000793087 SCV000932424 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 872 of the DSG2 protein (p.Glu872Gln). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is present in population databases (rs754057911, ExAC 0.002%). This variant has not been reported in the literature in individuals with DSG2-related disease. ClinVar contains an entry for this variant (Variation ID: 519349). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 Health, Inc RCV001191774 SCV001359674 uncertain significance Cardiomyopathy 2018-11-13 criteria provided, single submitter clinical testing

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