Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000480624 | SCV000569074 | uncertain significance | not provided | 2015-12-17 | criteria provided, single submitter | clinical testing | The V10I variant in the DEPDC5 gene has not been reported previously as a pathogenic variant, noras a benign variant, to our knowledge. The V10I variant was not observed at any significant frequencein approximately 6,100 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The V10Ivariant is a conservative amino acid substitution, which is not likely to impact secondary proteinstructure as these residues share similar properties. This substitution occurs at a position that isconserved across species. In silico analysis is inconsistent in its predictions as to whether or not thevariant is damaging to the protein structure/function. We interpret V10I as a variant of uncertainsignificance. |
Invitae | RCV000555417 | SCV000642184 | uncertain significance | Familial focal epilepsy with variable foci | 2019-06-11 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with isoleucine at codon 10 of the DEPDC5 protein (p.Val10Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs375027042, ExAC 0.01%). This variant has not been reported in the literature in individuals with DEPDC5-related disease. ClinVar contains an entry for this variant (Variation ID: 420294). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |