Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000794885 | SCV000934319 | uncertain significance | Imerslund-Gräsbeck syndrome | 2018-09-11 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 1131 of the CUBN protein (p.Thr1131Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs201138390, ExAC 0.06%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |