Submissions for variant NM_006231.4(POLE):c.296C>T (p.Pro99Leu)

gnomAD frequency: 0.00127  dbSNP: rs5744739

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000657106	SCV000289316	benign	not provided	2025-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000657106	SCV000293790	uncertain significance	not provided	2021-10-15	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with cancer undergoing multi-gene panel testing (Mandelker 2017); This variant is associated with the following publications: (PMID: 15766587, 28873162)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000657106	SCV000602022	benign	not provided	2019-06-18	criteria provided, single submitter	clinical testing
Mendelics	RCV000664291	SCV002519194	likely benign	Hereditary cancer-predisposing syndrome	2024-04-09	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000664291	SCV002536795	likely benign	Hereditary cancer-predisposing syndrome	2021-07-13	criteria provided, single submitter	curation
Ambry Genetics	RCV000664291	SCV005481513	benign	Hereditary cancer-predisposing syndrome	2024-08-20	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
True Health Diagnostics	RCV000664291	SCV000788173	uncertain significance	Hereditary cancer-predisposing syndrome	2017-10-26	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004532925	SCV004752307	likely benign	POLE-related disorder	2021-04-22	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).