Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ai |
RCV002223428 | SCV002501774 | uncertain significance | not provided | 2021-07-22 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002373049 | SCV002668757 | uncertain significance | Cardiovascular phenotype | 2024-09-30 | criteria provided, single submitter | clinical testing | The p.A241T variant (also known as c.721G>A), located in coding exon 7 of the DSG2 gene, results from a G to A substitution at nucleotide position 721. The alanine at codon 241 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 deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002481031 | SCV002783307 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003089161 | SCV003479764 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-03-26 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs371918777, gnomAD 0.01%). 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) 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. ClinVar contains an entry for this variant (Variation ID: 1677394). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 241 of the DSG2 protein (p.Ala241Thr). |
All of Us Research Program, |
RCV004005532 | SCV004834278 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2024-08-06 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with threonine at codon 241 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 2/248992 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. |