ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1178G>A (p.Ser393Asn)

dbSNP: rs2043024774
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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 RCV003770502 SCV001486065 uncertain significance not provided 2023-07-29 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. This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 393 of the POLE protein (p.Ser393Asn). 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: 1000886). 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.
Ambry Genetics RCV003294210 SCV003993351 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-08 criteria provided, single submitter clinical testing The p.S393N variant (also known as c.1178G>A), located in coding exon 12 of the POLE gene, results from a G to A substitution at nucleotide position 1178. The serine at codon 393 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. 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 RCV003770502 SCV005077994 uncertain significance not provided 2023-12-10 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: 20951805)

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