ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.6088C>T (p.Arg2030Ter)

gnomAD frequency: 0.00003  dbSNP: rs374417889
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001029890 SCV001592102 pathogenic Imerslund-Grasbeck syndrome 2020-02-28 criteria provided, single submitter clinical testing Loss-of-function variants in CUBN are known to be pathogenic (PMID: 15024727, 22929189). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with CUBN-related conditions. This variant is present in population databases (rs374417889, ExAC 0.02%). This sequence change creates a premature translational stop signal (p.Arg2030*) in the CUBN gene. It is expected to result in an absent or disrupted protein product.
Revvity Omics, Revvity RCV001784565 SCV002023990 pathogenic not provided 2023-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001784565 SCV002032420 pathogenic not provided 2024-08-05 criteria provided, single submitter clinical testing Identified with a second variant in unrelated patients with kidney disease in published literature (PMID: 31613795, 35064937); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15024727, 31613795, 22929189, 35064937)
Fulgent Genetics, Fulgent Genetics RCV002497349 SCV002814305 likely pathogenic Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2022-05-31 criteria provided, single submitter clinical testing
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV001029890 SCV001192681 likely pathogenic Imerslund-Grasbeck syndrome 2019-03-19 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003928668 SCV004741290 pathogenic CUBN-related disorder 2023-11-29 no assertion criteria provided clinical testing The CUBN c.6088C>T variant is predicted to result in premature protein termination (p.Arg2030*). This variant was reported with a second CUBN variant in two patients with kidney disease; however, phase of the variants was not determined (Supp. Table 2 in Bedin et al. 2020. PubMed ID: 31613795). Of note, the c.6088C>T has been reported with the c.5428C>T (p.Arg1810*) variant in two patients in the literature, but segregation analysis was not completed to determine phase (Family 21, Supp Table 2 in Bedin et al. 2020. PubMed ID: 31613795; Case #20, Supp. Table 3 in Lu L et al 2022. PubMed ID: 35064937). At PreventionGenetics, we have observed the c.6088C>T and c.5428C>T variants to occur on the same allele (cis phase) based on parental follow up testing (internal data). This variant is reported in 0.015% of alleles in individuals of East Asian descent in gnomAD, including one homozygous individual. Nonsense variants in CUBN are expected to be pathogenic. This variant is interpreted as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.