Submissions for variant NM_000038.6(APC):c.4055T>C (p.Val1352Ala)

gnomAD frequency: 0.00004  dbSNP: rs528724202

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129128	SCV000183846	benign	Hereditary cancer-predisposing syndrome	2021-05-21	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
GeneDx	RCV001704052	SCV000568279	likely benign	not provided	2018-05-02	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21859464, 18199528, 29069792, 27121310)
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000483615	SCV000600093	uncertain significance	not specified	2017-03-25	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129128	SCV000686963	uncertain significance	Hereditary cancer-predisposing syndrome	2022-11-08	criteria provided, single submitter	clinical testing	This missense variant replaces valine with alanine at codon 1352 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with colorectal cancer, non-medullary thyroid cancer, and colorectal adenomas (PMID: 18199528, 26530882, 27121310, 29069792, 31062380). This variant has also been identified in 17/282154 chromosomes (17/19940 East Asian chromosomes) in the general population by the Genome Aggregation Database (gnomAD) and has been reported in a non-cancer Korean cohort (PMID: 28706299). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae	RCV000646425	SCV000768197	likely benign	Familial adenomatous polyposis 1	2024-01-28	criteria provided, single submitter	clinical testing
Counsyl	RCV000646425	SCV000785305	uncertain significance	Familial adenomatous polyposis 1	2017-07-05	criteria provided, single submitter	clinical testing
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153412	SCV003843479	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000646425	SCV004018759	likely benign	Familial adenomatous polyposis 1	2023-02-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.