ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5866G>A (p.Glu1956Lys)

gnomAD frequency: 0.00001  dbSNP: rs749992643
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000482116 SCV000543995 uncertain significance not provided 2025-02-03 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1956 of the POLE protein (p.Glu1956Lys). This variant is present in population databases (rs749992643, 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: 405680). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 RCV000482116 SCV000569146 uncertain significance not provided 2023-10-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29056344)
Fulgent Genetics, Fulgent Genetics RCV000765046 SCV000896243 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome 2018-10-31 criteria provided, single submitter clinical testing
Mendelics RCV003492050 SCV002519021 likely benign Hereditary cancer 2024-01-23 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000482116 SCV003809181 uncertain significance not provided 2019-11-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV003168750 SCV003896824 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-07 criteria provided, single submitter clinical testing The c.5866G>A (p.E1956K) alteration is located in exon 43 (coding exon 43) of the POLE gene. This alteration results from a G to A substitution at nucleotide position 5866, causing the glutamic acid (E) at amino acid position 1956 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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