ClinVar Miner

Submissions for variant NM_001081.4(CUBN):c.3391A>G (p.Thr1131Ala)

gnomAD frequency: 0.00007  dbSNP: rs201138390
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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 RCV000794885 SCV000934319 uncertain significance Imerslund-Grasbeck syndrome 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 1131 of the CUBN protein (p.Thr1131Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs201138390, ExAC 0.06%). This variant has not been reported in the literature in individuals affected with CUBN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
GeneDx RCV001759499 SCV002007591 uncertain significance not provided 2019-11-19 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004027506 SCV004853442 likely benign Inborn genetic diseases 2024-10-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV005036140 SCV005669093 uncertain significance Imerslund-Grasbeck syndrome type 1; Proteinuria, chronic benign 2024-03-11 criteria provided, single submitter clinical testing

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