ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.3293C>G (p.Ser1098Cys) (rs2848673)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171907 SCV000050909 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000214180 SCV000271718 uncertain significance not specified 2015-03-11 criteria provided, single submitter clinical testing The p.Ser1098Cys variant in DSG2 has been reported at least 1 individual with AR VC or suspected ARVC (den Haan 2009), but has also been identified in 4/66638 Eu ropean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadi; dbSNP rs2848673). Serine at position 1098 is not conserved in evol ution and 2 mammalian species (bats) carry a cystine (Cys) at this position, rai sing the possibility that this change is tolerated. In summary, the clinical sig nificance of the p.Ser1098Cys variant is uncertain.
Color Health, Inc RCV001179560 SCV001344252 uncertain significance Cardiomyopathy 2019-10-04 criteria provided, single submitter clinical testing
Invitae RCV001223258 SCV001395397 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-08-17 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 1098 of the DSG2 protein (p.Ser1098Cys). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs2848673, ExAC 0.006%). This variant has not been reported in the literature in individuals with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 191633). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0. The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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