Submissions for variant NM_006231.4(POLE):c.4645C>G (p.Pro1549Ala)

dbSNP: rs147500308

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000760015	SCV000289395	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000507787	SCV000889757	benign	not specified	2017-08-22	criteria provided, single submitter	clinical testing
Mendelics	RCV000988933	SCV001138866	likely benign	Colorectal cancer, susceptibility to, 12	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000760015	SCV001473593	uncertain significance	not provided	2019-10-24	criteria provided, single submitter	clinical testing	The POLE c.4645C>G; p.Pro1549Ala variant (rs147500308), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 240531). This variant is found in the general population with an overall allele frequency of 0.04% (101/282144 alleles) in the Genome Aggregation Database. The proline at codon 1549 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, due to the lack of clinical and functional data, the clinical significance of this variant is uncertain at this time.
GeneDx	RCV000760015	SCV001820602	likely benign	not provided	2021-01-27	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002258857	SCV002536861	likely benign	Hereditary cancer-predisposing syndrome	2021-04-26	criteria provided, single submitter	curation
Revvity Omics, Revvity	RCV000760015	SCV004236432	uncertain significance	not provided	2023-03-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004532930	SCV004744508	likely benign	POLE-related disorder	2020-12-04	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).