ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.427A>C (p.Asn143His)

gnomAD frequency: 0.00015  dbSNP: rs151018922
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001344092 SCV001538128 uncertain significance Imerslund-Grasbeck syndrome 2022-07-29 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 143 of the CUBN protein (p.Asn143His). This variant is present in population databases (rs151018922, gnomAD 0.05%). 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: 1040445). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Fulgent Genetics, Fulgent Genetics RCV002499686 SCV002780440 uncertain significance Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2021-12-02 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003321828 SCV004026141 uncertain significance not provided 2022-12-14 criteria provided, single submitter clinical testing PP3, PM2_SUP
GeneDx RCV003321828 SCV005080421 uncertain significance not provided 2024-04-30 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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