Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002051279 | SCV002108487 | uncertain significance | Imerslund-Grasbeck syndrome | 2021-02-13 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs763563422, ExAC 0.01%). 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. 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. This variant has not been reported in the literature in individuals with CUBN-related conditions. This sequence change replaces arginine with cysteine at codon 1377 of the CUBN protein (p.Arg1377Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. |
| Fulgent Genetics, |
RCV002482430 | SCV002788592 | uncertain significance | Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign | 2021-10-27 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004611888 | SCV005104782 | uncertain significance | Inborn genetic diseases | 2024-05-12 | criteria provided, single submitter | clinical testing | The c.4129C>T (p.R1377C) alteration is located in exon 28 (coding exon 28) of the CUBN gene. This alteration results from a C to T substitution at nucleotide position 4129, causing the arginine (R) at amino acid position 1377 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |