Submissions for variant NM_006231.4(POLE):c.1308C>T (p.Pro436=)

gnomAD frequency: 0.00001  dbSNP: rs755627156

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000759262	SCV000653045	likely benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000561098	SCV000671240	likely benign	Hereditary cancer-predisposing syndrome	2016-04-06	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	RCV000759262	SCV000888491	likely benign	not provided	2021-05-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000759262	SCV001805530	uncertain significance	not provided	2019-01-08	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016; McVean et al., 2012; Exome Variant Server); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27149842)
Sema4, Sema4	RCV000561098	SCV002536743	likely benign	Hereditary cancer-predisposing syndrome	2020-10-16	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000759262	SCV004136758	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	POLE: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV004543215	SCV004773261	likely benign	POLE-related disorder	2020-02-10	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).