Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000826101 | SCV000967606 | likely pathogenic | Imerslund-Grasbeck syndrome | 2018-07-18 | criteria provided, single submitter | clinical testing | The p.Arg1487fs variant in CUBN has not been previously reported in individuals with Imerslund-Grasbeck syndrome or megaloblastic anemia, but has been identifie d in 7/126726 European chromosomes by the Genome Aggregation Database (gnomAD, h ttp://gnomad.broadinstitute.org; dbSNP rs770921101). Although this variant has b een seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is predicted to cause a frames hift, which alters the protein?s amino acid sequence beginning at position 1487 and leads to a premature termination codon 43 amino acids downstream. This alter ation is then predicted to lead to a truncated or absent protein. Loss of functi on of the CUBN gene is an established disease mechanism in autosomal recessive I merslund-Grasbeck syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic . ACMG/AMP criteria applied: PVS1, PM2 |
| Fulgent Genetics, |
RCV001535845 | SCV001752456 | pathogenic | Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign | 2021-06-30 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV001784460 | SCV002019778 | pathogenic | not provided | 2020-03-25 | criteria provided, single submitter | clinical testing |