ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1843A>G (p.Ser615Gly)

dbSNP: rs932588382
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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 RCV003540983 SCV000950248 uncertain significance not provided 2024-08-28 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 615 of the POLE protein (p.Ser615Gly). 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: 654162). 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%. 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 RCV004944190 SCV005484512 uncertain significance Hereditary cancer-predisposing syndrome 2024-07-16 criteria provided, single submitter clinical testing The c.1843A>G (p.S615G) alteration is located in exon 17 (coding exon 17) of the POLE gene. This alteration results from a A to G substitution at nucleotide position 1843, causing the serine (S) at amino acid position 615 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003540983 SCV005874624 uncertain significance not provided 2024-09-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20951805)

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