Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001330246 | SCV001521871 | uncertain significance | Imerslund-Grasbeck syndrome type 1 | 2020-06-20 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Invitae | RCV003770826 | SCV004681881 | uncertain significance | Imerslund-Grasbeck syndrome | 2023-04-13 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs755860454, gnomAD 0.008%). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CUBN protein function. ClinVar contains an entry for this variant (Variation ID: 1029049). This variant has not been reported in the literature in individuals affected with CUBN-related conditions. This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 89 of the CUBN protein (p.Lys89Gln). |