ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.550A>C (p.Ser184Arg)

dbSNP: rs1060500790
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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 RCV001764377 SCV000543951 uncertain significance not provided 2025-01-01 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 184 of the POLE protein (p.Ser184Arg). 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: 405640). 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.
GeneDx RCV001764377 SCV001998479 uncertain significance not provided 2023-12-06 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: 31068090)
Ambry Genetics RCV003168744 SCV003904030 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-18 criteria provided, single submitter clinical testing The p.S184R variant (also known as c.550A>C), located in coding exon 6 of the POLE gene, results from an A to C substitution at nucleotide position 550. The serine at codon 184 is replaced by arginine, an amino acid with dissimilar 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.

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