ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3934G>A (p.Ala1312Thr)

dbSNP: rs1565945759
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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 RCV001771999 SCV000832798 uncertain significance not provided 2023-03-09 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 1312 of the POLE protein (p.Ala1312Thr). 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: 580363). 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 not expected to disrupt POLE protein function. 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 RCV001771999 SCV002003260 uncertain significance not provided 2020-09-15 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); 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
Ambry Genetics RCV004026647 SCV005024571 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-26 criteria provided, single submitter clinical testing The p.A1312T variant (also known as c.3934G>A), located in coding exon 31 of the POLE gene, results from a G to A substitution at nucleotide position 3934. The alanine at codon 1312 is replaced by threonine, an amino acid with similar 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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