ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.4420C>T (p.Pro1474Ser)

gnomAD frequency: 0.00005  dbSNP: rs201251467
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001202018 SCV001373114 uncertain significance Imerslund-Grasbeck syndrome 2023-07-10 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1474 of the CUBN protein (p.Pro1474Ser). This variant is present in population databases (rs201251467, gnomAD 0.1%). 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: 933743). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
Fulgent Genetics, Fulgent Genetics RCV002491602 SCV002776689 uncertain significance Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2022-01-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV004033523 SCV004853448 uncertain significance Inborn genetic diseases 2023-11-21 criteria provided, single submitter clinical testing The c.4420C>T (p.P1474S) alteration is located in exon 30 (coding exon 30) of the CUBN gene. This alteration results from a C to T substitution at nucleotide position 4420, causing the proline (P) at amino acid position 1474 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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