ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5653G>A (p.Ala1885Thr)

gnomAD frequency: 0.00004  dbSNP: rs748008084
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000760025 SCV000544213 uncertain significance not provided 2024-12-28 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1885 of the POLE protein (p.Ala1885Thr). This variant is present in population databases (rs748008084, gnomAD 0.009%). This missense change has been observed in individual(s) with breast cancer (PMID: 33558524). ClinVar contains an entry for this variant (Variation ID: 405886). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760025 SCV000889772 uncertain significance not provided 2017-10-09 criteria provided, single submitter clinical testing
GeneDx RCV000760025 SCV001825408 uncertain significance not provided 2023-03-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer (Moradian et al., 2021); This variant is associated with the following publications: (PMID: 31034466, 33558524)
Genetics and Molecular Pathology, SA Pathology RCV000471957 SCV002556505 uncertain significance Colorectal cancer, susceptibility to, 12 2020-06-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV004943870 SCV005481526 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-17 criteria provided, single submitter clinical testing The p.A1885T variant (also known as c.5653G>A), located in coding exon 41 of the POLE gene, results from a G to A substitution at nucleotide position 5653. The alanine at codon 1885 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Center of Medical Genetics and Primary Health Care RCV001269354 SCV001448692 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing

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