Submissions for variant NM_000038.6(APC):c.1405C>T (p.Leu469=)

gnomAD frequency: 0.00003  dbSNP: rs746293695

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000587476	SCV000569661	uncertain significance	not provided	2018-10-16	criteria provided, single submitter	clinical testing	This variant is denoted APC c.1405C>T at the DNA level. This variant is silent at the coding level, preserving a Leucine at codon 469. In-silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. This variant was not observed at a significant allele frequency in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether APC c.1405C>T is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003766682	SCV000647173	likely benign	Familial adenomatous polyposis 1	2025-01-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000562539	SCV000667396	likely benign	Hereditary cancer-predisposing syndrome	2015-05-19	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000855609	SCV000693995	likely benign	not specified	2019-08-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000562539	SCV000909244	likely benign	Hereditary cancer-predisposing syndrome	2017-10-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587476	SCV004219646	likely benign	not provided	2022-12-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004003331	SCV004837395	likely benign	Classic or attenuated familial adenomatous polyposis	2023-12-13	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003766682	SCV004932098	benign	Familial adenomatous polyposis 1	2024-03-01	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.