ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.9667T>C (p.Tyr3223His)

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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 RCV003005320 SCV003302438 uncertain significance Imerslund-Grasbeck syndrome 2024-03-16 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 3223 of the CUBN protein (p.Tyr3223His). This variant is present in population databases (rs143533714, 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: 2085892). 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 not expected to disrupt CUBN protein function with a negative predictive value of 80%. 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003321966 SCV004026142 uncertain significance not provided 2022-12-14 criteria provided, single submitter clinical testing PM2_SUP
Ambry Genetics RCV004068494 SCV004854068 uncertain significance Inborn genetic diseases 2023-09-23 criteria provided, single submitter clinical testing The c.9667T>C (p.Y3223H) alteration is located in exon 61 (coding exon 61) of the CUBN gene. This alteration results from a T to C substitution at nucleotide position 9667, causing the tyrosine (Y) at amino acid position 3223 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005034572 SCV005668825 uncertain significance Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2024-02-27 criteria provided, single submitter clinical testing

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