Submissions for variant NM_006231.4(POLE):c.1357C>G (p.Gln453Glu)

gnomAD frequency: 0.00004  dbSNP: rs781360770

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000985945	SCV000544205	likely benign	not provided	2025-02-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000565048	SCV000671361	uncertain significance	Hereditary cancer-predisposing syndrome	2024-09-19	criteria provided, single submitter	clinical testing	The p.Q453E variant (also known as c.1357C>G), located in coding exon 13 of the POLE gene, results from a C to G substitution at nucleotide position 1357. The glutamine at codon 453 is replaced by glutamic acid, an amino acid with highly 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985945	SCV001134678	uncertain significance	not provided	2019-04-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000985945	SCV001819464	uncertain significance	not provided	2023-07-11	criteria provided, single submitter	clinical testing	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: 25032700, 29056344, 20951805)
Sema4, Sema4	RCV000565048	SCV002536748	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-07	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002268070	SCV002550185	uncertain significance	not specified	2025-03-04	criteria provided, single submitter	clinical testing