ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.6068C>A (p.Thr2023Asn) (rs771628123)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768287 SCV000898891 uncertain significance Facial dysmorphism, immunodeficiency, livedo, and short stature 2018-03-13 criteria provided, single submitter clinical testing POLE NM_006231.3 exon 44 p.Thr2023Asn (c.6068C>A): This variant has not been reported in the literature but is present in 2/33552 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs771628123). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV000808998 SCV000949132 uncertain significance Colorectal cancer, susceptibility to, 12 2018-11-28 criteria provided, single submitter clinical testing This sequence change replaces threonine with asparagine at codon 2023 of the POLE protein (p.Thr2023Asn). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and asparagine. This variant is present in population databases (rs771628123, ExAC 0.02%). This variant has not been reported in the literature in individuals with POLE-related disease. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760029 SCV000889779 uncertain significance not provided 2018-04-07 criteria provided, single submitter clinical testing

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