ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.856C>T (p.Pro286Ser)

dbSNP: rs1057519944
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003679003 SCV004423220 uncertain significance not provided 2023-01-06 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 variant disrupts the p.Pro286 amino acid residue in POLE. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32424176). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt POLE protein function. ClinVar contains an entry for this variant (Variation ID: 376501). 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 serine, which is neutral and polar, at codon 286 of the POLE protein (p.Pro286Ser).
Database of Curated Mutations (DoCM) RCV000436940 SCV000507151 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419260 SCV000507152 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429545 SCV000507153 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436302 SCV000507154 likely pathogenic Uterine carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418641 SCV000507155 likely pathogenic Pancreatic adenocarcinoma 2016-05-31 no assertion criteria provided literature only

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