Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000155683 | SCV000205393 | uncertain significance | not specified | 2013-04-21 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Val467Ile varia nt in DSG2 has not been reported in individuals with cardiomyopathy or in large population studies. Valine (Val) at position 467 is not conserved in mammals and evolutionarily distant species, and marmoset carries an isoleucine (Ile; this v ariant) at this position, raising the possibility that this change may be tolera ted. Additional computational analyses (biochemical amino acid properties, Align GVGD, PolyPhen2, and SIFT) suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Alt hough the high lack of conservation and the presence of this variant in another primate support that the Val467Ile variant may be benign, additional studies are needed to fully assess its clinical significance. |
| Invitae | RCV002516134 | SCV003505679 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-01-28 | criteria provided, single submitter | clinical testing | 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) performed at Invitae indicates that this missense variant is not expected to disrupt DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 178910). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 467 of the DSG2 protein (p.Val467Ile). |