Submissions for variant NM_006231.4(POLE):c.3777C>T (p.Pro1259=)

gnomAD frequency: 0.00002  dbSNP: rs770904877

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000423793	SCV000531875	likely benign	not specified	2016-09-16	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003401431	SCV000653238	likely benign	not provided	2025-01-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000570281	SCV000671296	likely benign	Hereditary cancer-predisposing syndrome	2016-04-26	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.
Sema4, Sema4	RCV000570281	SCV002536824	likely benign	Hereditary cancer-predisposing syndrome	2021-04-19	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV003401431	SCV004136748	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	POLE: BP4, BP7
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV005235290	SCV005881081	benign	Colorectal cancer, susceptibility to, 12	2025-02-01	criteria provided, single submitter	clinical testing