ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.6728C>T (p.Pro2243Leu)

gnomAD frequency: 0.00001  dbSNP: rs544059289
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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 RCV000702158 SCV000830999 uncertain significance Imerslund-Grasbeck syndrome 2018-06-14 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CUBN-related disease. This variant is present in population databases (rs544059289, ExAC 0.01%). This sequence change replaces proline with leucine at codon 2243 of the CUBN protein (p.Pro2243Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine.
Fulgent Genetics, Fulgent Genetics RCV002477618 SCV002788999 uncertain significance Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2022-04-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV004026585 SCV004854045 uncertain significance Inborn genetic diseases 2024-01-23 criteria provided, single submitter clinical testing The c.6728C>T (p.P2243L) alteration is located in exon 44 (coding exon 44) of the CUBN gene. This alteration results from a C to T substitution at nucleotide position 6728, causing the proline (P) at amino acid position 2243 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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