ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.179C>T (p.Thr60Ile)

gnomAD frequency: 0.00006  dbSNP: rs772684226
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003656431 SCV001236000 uncertain significance not provided 2024-10-02 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 60 of the POLE protein (p.Thr60Ile). This variant is present in population databases (rs772684226, gnomAD 0.03%). 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: 863703). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt POLE protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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.
Ambry Genetics RCV002402477 SCV002710734 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-15 criteria provided, single submitter clinical testing The p.T60I variant (also known as c.179C>T), located in coding exon 2 of the POLE gene, results from a C to T substitution at nucleotide position 179. The threonine at codon 60 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003656431 SCV005388531 uncertain significance not provided 2024-04-11 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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