ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3382C>G (p.Leu1128Val)

dbSNP: rs755839896
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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 RCV001766548 SCV000832440 uncertain significance not provided 2023-04-27 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POLE protein function. ClinVar contains an entry for this variant (Variation ID: 580093). This variant has not been reported in the literature in individuals affected with POLE-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1128 of the POLE protein (p.Leu1128Val).
GeneDx RCV001766548 SCV001999832 uncertain significance not provided 2019-12-05 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004944125 SCV005478937 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-29 criteria provided, single submitter clinical testing The p.L1128V variant (also known as c.3382C>G), located in coding exon 28 of the POLE gene, results from a C to G substitution at nucleotide position 3382. The leucine at codon 1128 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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