Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000815464 | SCV000955918 | uncertain significance | Imerslund-Grasbeck syndrome | 2022-11-29 | criteria provided, single submitter | clinical testing | 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CUBN protein function. ClinVar contains an entry for this variant (Variation ID: 658610). This variant has not been reported in the literature in individuals affected with CUBN-related conditions. This variant is present in population databases (rs377159715, gnomAD 0.04%). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 2894 of the CUBN protein (p.Pro2894Ala). |
Fulgent Genetics, |
RCV002478897 | SCV002788347 | uncertain significance | Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign | 2024-04-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003243327 | SCV003940836 | uncertain significance | Inborn genetic diseases | 2023-05-15 | criteria provided, single submitter | clinical testing | The c.8680C>G (p.P2894A) alteration is located in exon 55 (coding exon 55) of the CUBN gene. This alteration results from a C to G substitution at nucleotide position 8680, causing the proline (P) at amino acid position 2894 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |