ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.4889G>A (p.Arg1630Gln)

gnomAD frequency: 0.00009  dbSNP: rs750180239
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001551413 SCV000772640 uncertain significance not provided 2025-01-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1630 of the POLE protein (p.Arg1630Gln). This variant is present in population databases (rs750180239, gnomAD 0.01%). 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: 540689). 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 RCV001551413 SCV001771922 uncertain significance not provided 2022-06-29 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004659149 SCV005154324 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-06 criteria provided, single submitter clinical testing The c.4889G>A (p.R1630Q) alteration is located in exon 37 (coding exon 37) of the POLE gene. This alteration results from a G to A substitution at nucleotide position 4889, causing the arginine (R) at amino acid position 1630 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV005231236 SCV005872699 uncertain significance not specified 2025-03-04 criteria provided, single submitter clinical testing

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