ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5390G>T (p.Ser1797Ile)

gnomAD frequency: 0.00001  dbSNP: rs749755939
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001598577 SCV001830667 uncertain significance not provided 2020-01-22 criteria provided, single submitter clinical testing 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
Labcorp Genetics (formerly Invitae), Labcorp RCV001598577 SCV002111793 uncertain significance not provided 2023-10-08 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1797 of the POLE protein (p.Ser1797Ile). This variant is not present in population databases (gnomAD no frequency). 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: 1223568). 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. 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 RCV002343779 SCV002642823 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-23 criteria provided, single submitter clinical testing The p.S1797I variant (also known as c.5390G>T), located in coding exon 40 of the POLE gene, results from a G to T substitution at nucleotide position 5390. The serine at codon 1797 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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