Submissions for variant NM_006231.4(POLE):c.2262C>T (p.Tyr754=)

gnomAD frequency: 0.00006  dbSNP: rs145337550

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000431002	SCV000522235	likely benign	not specified	2018-02-27	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	RCV000759275	SCV000556382	likely benign	not provided	2025-01-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000565470	SCV000671298	likely benign	Hereditary cancer-predisposing syndrome	2015-08-30	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759275	SCV000888512	benign	not provided	2018-01-16	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000565470	SCV002536781	benign	Hereditary cancer-predisposing syndrome	2021-05-21	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000431002	SCV005888381	likely benign	not specified	2025-01-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004533009	SCV004714217	likely benign	POLE-related disorder	2020-09-02	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).