ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.970C>G (p.Pro324Ala)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002387027 SCV002695215 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-23 criteria provided, single submitter clinical testing The p.P324A variant (also known as c.970C>G), located in coding exon 10 of the POLE gene, results from a C to G substitution at nucleotide position 970. The proline at codon 324 is replaced by alanine, an amino acid with highly similar 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003222427 SCV003302981 uncertain significance not provided 2022-01-17 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 324 of the POLE protein (p.Pro324Ala).
GeneDx RCV003222427 SCV003918532 uncertain significance not provided 2022-10-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on 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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