ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.6068C>A (p.Thr2023Asn)

dbSNP: rs771628123
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760029 SCV000889779 uncertain significance not provided 2018-04-07 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768287 SCV000898891 uncertain significance Facial dysmorphism-immunodeficiency-livedo-short stature syndrome 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000760029 SCV000949132 uncertain significance not provided 2024-10-20 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 2023 of the POLE protein (p.Thr2023Asn). This variant is present in population databases (rs771628123, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 619906). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV000760029 SCV001823319 uncertain significance not provided 2023-09-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 29056344)
Ambry Genetics RCV004027170 SCV003874624 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-04 criteria provided, single submitter clinical testing The p.T2023N variant (also known as c.6068C>A), located in coding exon 44 of the POLE gene, results from a C to A substitution at nucleotide position 6068. The threonine at codon 2023 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224386 SCV003920342 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 2021-12-22 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.
Fulgent Genetics, Fulgent Genetics RCV003224386 SCV005633670 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 2024-05-04 criteria provided, single submitter clinical testing

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