Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV001256689 | SCV001433087 | uncertain significance | Dilated cardiomyopathy 1A | 2020-02-12 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001301692 | SCV001490870 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 923 of the DSG2 protein (p.Pro923Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 978279). 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. |
Fulgent Genetics, |
RCV002491864 | SCV002781240 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2022-04-22 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV003532922 | SCV004363227 | uncertain significance | Cardiomyopathy | 2023-10-25 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 923 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 cardiovascular disorders in the literature. This variant has been identified in 1/249156 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. |
All of Us Research Program, |
RCV004004923 | SCV004821838 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 923 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 cardiovascular disorders in the literature. This variant has been identified in 1/249156 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. |
Ambry Genetics | RCV004619595 | SCV005117155 | uncertain significance | Cardiovascular phenotype | 2024-05-29 | criteria provided, single submitter | clinical testing | The c.2768C>G (p.P923R) alteration is located in exon 15 (coding exon 15) of the DSG2 gene. This alteration results from a C to G substitution at nucleotide position 2768, causing the proline (P) at amino acid position 923 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |