Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001874780 | SCV002144416 | uncertain significance | Imerslund-Grasbeck syndrome | 2022-08-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1166 of the CUBN protein (p.Gly1166Arg). This variant is present in population databases (rs201443885, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CUBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1372722). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Athena Diagnostics | RCV002506933 | SCV002817268 | uncertain significance | not provided | 2020-01-08 | criteria provided, single submitter | clinical testing | This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study. |
Ambry Genetics | RCV002551673 | SCV003744348 | uncertain significance | Inborn genetic diseases | 2022-12-19 | criteria provided, single submitter | clinical testing | The c.3496G>A (p.G1166R) alteration is located in exon 25 (coding exon 25) of the CUBN gene. This alteration results from a G to A substitution at nucleotide position 3496, causing the glycine (G) at amino acid position 1166 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV005040455 | SCV005669076 | uncertain significance | Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign | 2024-01-24 | criteria provided, single submitter | clinical testing |