ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.4906C>T (p.Arg1636Trp)

gnomAD frequency: 0.00001  dbSNP: rs551594427
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001211586 SCV001383131 uncertain significance Imerslund-Grasbeck syndrome 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1636 of the CUBN protein (p.Arg1636Trp). This variant is present in population databases (rs551594427, gnomAD 0.08%). 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: 941735). 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.
Ambry Genetics RCV002562375 SCV003745790 uncertain significance Inborn genetic diseases 2022-05-06 criteria provided, single submitter clinical testing The c.4906C>T (p.R1636W) alteration is located in exon 33 (coding exon 33) of the CUBN gene. This alteration results from a C to T substitution at nucleotide position 4906, causing the arginine (R) at amino acid position 1636 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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