Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000039417 | SCV000063101 | uncertain significance | not specified | 2012-11-07 | criteria provided, single submitter | clinical testing | The Lys694Asn variant in DSC2 has not been reported in the literature nor previo usly identified by our laboratory. This variant has not been identified in large and broad European American and African American populations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT ) suggest that the variant may not impact the protein, though this information i s not predictive enough to rule out pathogenicity. In summary, additional inform ation is needed to fully assess the variant's clinical significance. |
| Invitae | RCV002513544 | SCV003007144 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-07-06 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 46176). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs397517397, gnomAD 0.0009%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 694 of the DSC2 protein (p.Lys694Asn). |