ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.2963C>T (p.Ser988Leu)

gnomAD frequency: 0.00001  dbSNP: rs138391248
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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 RCV001552555 SCV000543887 uncertain significance not provided 2024-12-24 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 988 of the POLE protein (p.Ser988Leu). This variant is present in population databases (rs138391248, 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: 405581). 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.
GeneDx RCV001552555 SCV001773261 uncertain significance not provided 2024-04-23 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
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000474859 SCV003806954 uncertain significance Colorectal cancer, susceptibility to, 12 2022-08-17 criteria provided, single submitter clinical testing ACMG classification criteria: PM2 supporting
Clinical Genetics Laboratory, Skane University Hospital Lund RCV001552555 SCV005197238 uncertain significance not provided 2022-07-12 criteria provided, single submitter clinical testing

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