Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000480826 | SCV000568158 | uncertain significance | not provided | 2022-05-27 | criteria provided, single submitter | clinical testing | Reported as "likely to have pathogenic effects" in a review paper of desmosomal proteins which did not provide additional information (Al-Jassar et al., 2013); however, it has not been reported in association with DSG2-related disorders; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31402444, 23911551) |
Labcorp Genetics |
RCV000702467 | SCV000831323 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-11-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 157 of the DSG2 protein (p.Pro157Leu). This variant is present in population databases (rs587782938, 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: 155784). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSG2 protein function. 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. |
Color Diagnostics, |
RCV001190411 | SCV001357891 | uncertain significance | Cardiomyopathy | 2023-05-10 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 157 of the DSG2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 5/249312 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, |
RCV000143881 | SCV004819446 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-12-01 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 157 of the DSG2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 5/249312 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. |
Blueprint Genetics | RCV000143881 | SCV000188750 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2014-01-29 | no assertion criteria provided | clinical testing |