ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2111T>C (p.Ile704Thr)

gnomAD frequency: 0.00001  dbSNP: rs759420598
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001179462 SCV001344124 uncertain significance Cardiomyopathy 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with threonine at codon 704 of the DSG2 protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/249446 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001361742 SCV001557729 uncertain significance Arrhythmogenic right ventricular dysplasia 10 2023-01-28 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 920612). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs759420598, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 704 of the DSG2 protein (p.Ile704Thr).
Ambry Genetics RCV004994277 SCV005575794 uncertain significance Cardiovascular phenotype 2024-11-30 criteria provided, single submitter clinical testing The p.I704T variant (also known as c.2111T>C), located in coding exon 14 of the DSG2 gene, results from a T to C substitution at nucleotide position 2111. The isoleucine at codon 704 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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