ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.6095G>A (p.Cys2032Tyr)

gnomAD frequency: 0.00003  dbSNP: rs201720797
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center of Genomic medicine, Geneva, University Hospital of Geneva RCV000857246 SCV000999833 likely pathogenic Imerslund-Grasbeck syndrome 2019-03-18 criteria provided, single submitter clinical testing This variant was identified in combination with a second variant in trans in the same gene (CUBN - composite heterozygosity) in a patient with proteinuria and glomerulopathy
GeneDx RCV001776065 SCV002012659 uncertain significance not provided 2019-08-10 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV000857246 SCV002270977 uncertain significance Imerslund-Grasbeck syndrome 2022-10-31 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 2032 of the CUBN protein (p.Cys2032Tyr). This variant is present in population databases (rs201720797, gnomAD 0.02%). 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: 695032). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CUBN protein function. 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.
Eurofins-Biomnis RCV003236590 SCV003935130 likely pathogenic Proteinuria, chronic benign 2022-12-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005036241 SCV005673149 uncertain significance Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2024-06-11 criteria provided, single submitter clinical testing

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