Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000726268 | SCV000343302 | uncertain significance | not provided | 2016-07-19 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000726268 | SCV000536247 | uncertain significance | not provided | 2017-01-26 | criteria provided, single submitter | clinical testing | The S484G variant in the CUBN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The S484G variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S484G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Serine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret S484G as a variant of uncertain significance. |
| Labcorp Genetics |
RCV001850436 | SCV002119442 | uncertain significance | Imerslund-Grasbeck syndrome | 2022-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 484 of the CUBN protein (p.Ser484Gly). This variant is present in population databases (rs750735519, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with CUBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 289030). 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: "Possibly 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. |
| Fulgent Genetics, |
RCV002504013 | SCV002817102 | uncertain significance | Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign | 2022-04-15 | criteria provided, single submitter | clinical testing |