ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.3725C>T (p.Ser1242Phe)

gnomAD frequency: 0.00009  dbSNP: rs373213156
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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 RCV001662587 SCV000653234 uncertain significance not provided 2025-01-11 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1242 of the POLE protein (p.Ser1242Phe). This variant is present in population databases (rs373213156, gnomAD 0.02%). 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: 473618). 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 RCV001662587 SCV001872912 uncertain significance not provided 2024-11-18 criteria provided, single submitter clinical testing 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
Breakthrough Genomics, Breakthrough Genomics RCV001662587 SCV005192065 uncertain significance not provided criteria provided, single submitter not provided

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