ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.3649A>G (p.Asn1217Asp)

gnomAD frequency: 0.00003  dbSNP: rs778837015
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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 RCV002607230 SCV003507608 uncertain significance Imerslund-Grasbeck syndrome 2023-08-30 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. 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. ClinVar contains an entry for this variant (Variation ID: 2189271). This variant has not been reported in the literature in individuals affected with CUBN-related conditions. This variant is present in population databases (rs778837015, gnomAD 0.006%). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 1217 of the CUBN protein (p.Asn1217Asp).
GeneDx RCV003149054 SCV003836953 uncertain significance not provided 2022-08-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004614378 SCV005104779 uncertain significance Inborn genetic diseases 2024-06-16 criteria provided, single submitter clinical testing The c.3649A>G (p.N1217D) alteration is located in exon 25 (coding exon 25) of the CUBN gene. This alteration results from a A to G substitution at nucleotide position 3649, causing the asparagine (N) at amino acid position 1217 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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