ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.7976T>C (p.Val2659Ala)

gnomAD frequency: 0.00004  dbSNP: rs1007248288
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001339015 SCV001532730 uncertain significance Imerslund-Grasbeck syndrome 2020-09-15 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 2659 of the CUBN protein (p.Val2659Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CUBN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Fulgent Genetics, Fulgent Genetics RCV002493740 SCV002780194 uncertain significance Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2021-07-27 criteria provided, single submitter clinical testing
GeneDx RCV004774411 SCV005384876 uncertain significance not provided 2024-02-26 criteria provided, single submitter clinical testing 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
PreventionGenetics, part of Exact Sciences RCV003898322 SCV004710180 uncertain significance CUBN-related disorder 2024-01-04 no assertion criteria provided clinical testing The CUBN c.7976T>C variant is predicted to result in the amino acid substitution p.Val2659Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD. 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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