Submissions for variant NM_006231.4(POLE):c.2602C>T (p.Leu868=)

gnomAD frequency: 0.00035  dbSNP: rs115830215

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000759991	SCV000289301	benign	not provided	2025-01-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000759991	SCV000526465	likely benign	not provided	2021-04-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000563911	SCV000671332	likely benign	Hereditary cancer-predisposing syndrome	2015-06-28	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Mendelics	RCV004701320	SCV000838697	likely benign	Hereditary cancer	2024-09-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following: it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease, and/or has normal protein function, and/or has lack of segregation with disease, and/or has been detected in co-occurrence with known pathogenic variant, and/or has lack of disease association in case-control studies, and/or is located in a region inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000426433	SCV000889731	benign	not specified	2018-07-10	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001080224	SCV004016707	benign	Colorectal cancer, susceptibility to, 12	2023-07-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004532923	SCV004723191	likely benign	POLE-related disorder	2019-06-12	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).