ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.7106G>T (p.Gly2369Val)

gnomAD frequency: 0.00006  dbSNP: rs200593316
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000265602 SCV000361668 uncertain significance Imerslund-Grasbeck syndrome type 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Fulgent Genetics, Fulgent Genetics RCV002480085 SCV002794530 uncertain significance Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2021-10-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003505104 SCV004279087 uncertain significance Imerslund-Grasbeck syndrome 2022-11-04 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: 299427). This variant has not been reported in the literature in individuals affected with CUBN-related conditions. This variant is present in population databases (rs200593316, gnomAD 0.2%). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2369 of the CUBN protein (p.Gly2369Val).
Ambry Genetics RCV004021469 SCV004854049 uncertain significance Inborn genetic diseases 2023-11-28 criteria provided, single submitter clinical testing The c.7106G>T (p.G2369V) alteration is located in exon 46 (coding exon 46) of the CUBN gene. This alteration results from a G to T substitution at nucleotide position 7106, causing the glycine (G) at amino acid position 2369 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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