ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.98A>C (p.Asn33Thr)

dbSNP: rs727505205
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156698 SCV000206419 uncertain significance not specified 2014-07-25 criteria provided, single submitter clinical testing The Asn33Thr variant in DSG2 has not been previously reported in individuals wit h cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In s ummary, the clinical significance of the Asn33Thr variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV001296337 SCV001485297 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 33 of the DSG2 protein (p.Asn33Thr). This variant is present in population databases (rs727505205, gnomAD 0.05%). 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: 179897). 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 with a negative predictive value of 95%. 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.
Ambry Genetics RCV002381504 SCV002693264 uncertain significance Cardiovascular phenotype 2021-03-07 criteria provided, single submitter clinical testing The p.N33T variant (also known as c.98A>C), located in coding exon 3 of the DSG2 gene, results from an A to C substitution at nucleotide position 98. This alteration was identified in one patient with dilated cardiomyopathy (DCM) in a large study of pathogenicity of Mendelian variants in cardiomyopathy patients, but clinical details are limited (Walsh R et al. Genet Med, 2017 02;19:192-203). The asparagine at codon 33 is replaced by threonine, an amino acid with 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.
Fulgent Genetics, Fulgent Genetics RCV002484955 SCV002784310 uncertain significance Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB 2021-08-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000156698 SCV004122609 uncertain significance not specified 2023-10-09 criteria provided, single submitter clinical testing

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