Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000321365 | SCV000329945 | pathogenic | not provided | 2018-04-10 | criteria provided, single submitter | clinical testing | The c.1865delC pathogenic variant in the CUBN gene has been reported previously, with another variant, in association with inherited cobalamin malabsorption (Tanner et al., 2012). The c.1865delC variant causes a frameshift starting with codon Threonine 622, changes this amino acid to a Isoleucine residue, and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Thr622IlefsX7. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1865delC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1865delC as a pathogenic variant. |
| Eurofins Ntd Llc |
RCV000321365 | SCV000861332 | pathogenic | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000321365 | SCV001472127 | pathogenic | not provided | 2019-08-23 | criteria provided, single submitter | clinical testing | The CUBN c.1865delC; p.Thr622fs variant (rs386833771) is reported in the literature in an individual affected with a hereditary vitamin B12 deficiency syndrome that also carried a second frameshift variant (Tanner 2012). The c.1865delC variant is found on only three chromosomes in the Genome Aggregation Database (3/282742 alleles), indicating it is not a common polymorphism. This variant causes a frameshift by deleting a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Tanner SM et al. Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns. Orphanet J Rare Dis. 2012 Aug 28;7:56. |
| Fulgent Genetics, |
RCV002496724 | SCV002810302 | pathogenic | Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign | 2024-05-06 | criteria provided, single submitter | clinical testing | |
| Juha Muilu Group; Institute for Molecular Medicine Finland |
RCV000049735 | SCV000082142 | probable-pathogenic | Imerslund-Grasbeck syndrome | no assertion criteria provided | not provided | Converted during submission to Likely pathogenic. |