ClinVar Miner

Submissions for variant NM_001081.3(CUBN):c.6268A>G (p.Lys2090Glu) (rs201374966)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506914 SCV000603284 uncertain significance not provided 2017-05-25 criteria provided, single submitter clinical testing The p.Lys2090Glu variant (rs201374966) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Exome Aggregation Consortium Browser with an overall population frequency of 0.009 percent (identified on 11 out of 121,202 chromosomes). The lysine at position 2090 is highly conserved, up to Cow (considering 10 species) (Alamut v2.9.0) and computational analyses of the effects of the p.Lys2090Glu variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Lys2090Glu variant with certainty.
Invitae RCV001215712 SCV001387472 uncertain significance Imerslund-Gräsbeck syndrome 2019-05-06 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 2090 of the CUBN protein (p.Lys2090Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs201374966, ExAC 0.02%). This variant has not been reported in the literature in individuals with CUBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 439587). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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