ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.4229A>C (p.His1410Pro)

dbSNP: rs1313711311
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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 RCV000585128 SCV000653276 uncertain significance not provided 2024-12-22 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1410 of the POLE protein (p.His1410Pro). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 473656). 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 expected to disrupt POLE protein function with a positive 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.
CeGaT Center for Human Genetics Tuebingen RCV000585128 SCV000692766 uncertain significance not provided 2017-10-01 criteria provided, single submitter clinical testing
GeneDx RCV000585128 SCV001738280 uncertain significance not provided 2019-12-20 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016) In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect Has not been previously published as a pathogenic or benign germline variant to our knowledge This variant is associated with the following publications: (PMID: 29056344)
Breakthrough Genomics, Breakthrough Genomics RCV000585128 SCV005192062 uncertain significance not provided criteria provided, single submitter not provided

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