Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000689499 | SCV000817153 | uncertain significance | Imerslund-Gräsbeck syndrome | 2018-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 667 of the CUBN protein (p.Thr667Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs141089159, ExAC 0.009%). 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: "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. |