Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000150549 | SCV000197778 | uncertain significance | not specified | 2014-01-07 | criteria provided, single submitter | clinical testing | The Asn1043Lys variant in DSG2 has not been reported in individuals with cardiom yopathy or in large population studies. Computational analyses (biochemical amin o acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that th is variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Additional information is needed to fully ass ess the clinical significance of the Asn1043Lys variant. |
Labcorp Genetics |
RCV001850045 | SCV002196304 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1043 of the DSG2 protein (p.Asn1043Lys). This variant is present in population databases (rs727502992, gnomAD 0.02%). 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: 163224). 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 | RCV003162610 | SCV003859070 | uncertain significance | Cardiovascular phenotype | 2022-11-04 | criteria provided, single submitter | clinical testing | The p.N1043K variant (also known as c.3129T>G), located in coding exon 15 of the DSG2 gene, results from a T to G substitution at nucleotide position 3129. The asparagine at codon 1043 is replaced by lysine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV003998195 | SCV004822301 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-08-15 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with lysine at codon 1043 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 been identified in 2/31406 chromosomes 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. |