Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000705399 | SCV000834394 | uncertain significance | Imerslund-Gräsbeck syndrome | 2018-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with proline at codon 2464 of the CUBN protein (p.Thr2464Pro). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and proline. This variant is present in population databases (rs769747844, ExAC 0.05%). This variant has not been reported in the literature in individuals with CUBN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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. |