ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.4459C>T (p.Arg1487Ter)

gnomAD frequency: 0.00016  dbSNP: rs145661597
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000698044 SCV000826685 pathogenic Imerslund-Grasbeck syndrome 2024-10-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1487*) in the CUBN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CUBN are known to be pathogenic (PMID: 15024727, 22929189, 25349199, 31613795, 34979989). This variant is present in population databases (rs145661597, gnomAD 0.01%). 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: 575738). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV004721561 SCV005327900 likely pathogenic not provided 2024-03-12 criteria provided, single submitter clinical testing Reported with a second variant (phase unknown) in a patient with renal disease in published literature (PMID: 31613795); 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: 31613795, 25635822)
Fulgent Genetics, Fulgent Genetics RCV005034310 SCV005668621 pathogenic Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2024-04-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV005357933 SCV005912712 likely pathogenic Imerslund-Grasbeck syndrome type 1 2023-09-18 criteria provided, single submitter research
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV000698044 SCV001192691 pathogenic Imerslund-Grasbeck syndrome 2019-03-26 no assertion criteria provided clinical testing

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