ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1138G>A (p.Gly380Ser)

dbSNP: rs199746481
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003153726 SCV000653030 uncertain significance not provided 2024-11-06 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 380 of the POLE protein (p.Gly380Ser). This variant is present in population databases (rs199746481, 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: 473437). 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.
Ambry Genetics RCV000568326 SCV000671390 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-03 criteria provided, single submitter clinical testing The p.G380S variant (also known as c.1138G>A), located in coding exon 12 of the POLE gene, results from a G to A substitution at nucleotide position 1138. The glycine at codon 380 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002465710 SCV002760932 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
GeneDx RCV003153726 SCV003842545 uncertain significance not provided 2023-03-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29056344, 20951805)
Baylor Genetics RCV004569067 SCV005056548 uncertain significance Colorectal cancer, susceptibility to, 12 2024-01-24 criteria provided, single submitter clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund RCV003153726 SCV005197242 uncertain significance not provided 2022-05-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005004230 SCV005633763 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 2024-03-24 criteria provided, single submitter clinical testing

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