ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.6260C>G (p.Ser2087Cys)

gnomAD frequency: 0.00016  dbSNP: rs376641725
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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 RCV001873944 SCV002108808 uncertain significance Imerslund-Grasbeck syndrome 2023-09-13 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 expected to disrupt CUBN protein function. ClinVar contains an entry for this variant (Variation ID: 1353782). This variant has not been reported in the literature in individuals affected with CUBN-related conditions. This variant is present in population databases (rs376641725, gnomAD 0.04%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2087 of the CUBN protein (p.Ser2087Cys).
Fulgent Genetics, Fulgent Genetics RCV002478112 SCV002787711 uncertain significance Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2022-03-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003416502 SCV004115340 uncertain significance CUBN-related disorder 2022-08-19 criteria provided, single submitter clinical testing The CUBN c.6260C>G variant is predicted to result in the amino acid substitution p.Ser2087Cys. This variant was reported in a patient with elevated methylmalonic acid and non-compaction cardiomyopathy; however, this patient also had two additional variants in CUBN and the phase was not determined (Patient 9, Pupavac et al 2016. PubMed ID: 26827111). This variant is reported in 0.040% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-16970167-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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