ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1591G>A (p.Gly531Arg)

gnomAD frequency: 0.00001  dbSNP: rs748489355
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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 RCV000985950 SCV000289261 uncertain significance not provided 2024-10-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 531 of the POLE protein (p.Gly531Arg). This variant is present in population databases (rs748489355, gnomAD 0.004%). 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: 240398). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985950 SCV001134683 uncertain significance not provided 2019-05-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV002401897 SCV002709704 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-30 criteria provided, single submitter clinical testing The p.G531R variant (also known as c.1591G>A), located in coding exon 15 of the POLE gene, results from a G to A substitution at nucleotide position 1591. The glycine at codon 531 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. 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.
Fulgent Genetics, Fulgent Genetics RCV005008190 SCV005633758 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 2024-06-07 criteria provided, single submitter clinical testing

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