Submissions for variant NM_000038.6(APC):c.385G>C (p.Glu129Gln)

gnomAD frequency: 0.00005  dbSNP: rs376628500

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000196705	SCV000254011	benign	Familial adenomatous polyposis 1	2025-01-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000216893	SCV000273092	likely benign	Hereditary cancer-predisposing syndrome	2019-11-18	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.
Counsyl	RCV000196705	SCV000489348	uncertain significance	Familial adenomatous polyposis 1	2016-09-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000589545	SCV000490404	likely benign	not provided	2019-05-29	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24728327, 28615371, 29753010, 30093976)
Color Diagnostics, LLC DBA Color Health	RCV000216893	SCV000681635	likely benign	Hereditary cancer-predisposing syndrome	2020-04-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000120050	SCV000694039	likely benign	not specified	2024-07-08	criteria provided, single submitter	clinical testing	Variant summary: APC c.385G>C (p.Glu129Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.1e-05 in 252804 control chromosomes (gnomAD and Bodian_2014). The observed variant frequency is approximately 1 fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05). c.385G>C has been reported in the literature in individuals affected with Familial Adenomatous Polyposis, without strong evidence for causality (Chan_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 24728327, 30093976). ClinVar contains an entry for this variant (Variation ID: 133539). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000589545	SCV001470644	likely benign	not provided	2019-12-13	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000216893	SCV002536137	likely benign	Hereditary cancer-predisposing syndrome	2022-01-06	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000196705	SCV004018773	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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000120050	SCV004025026	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005359132	SCV005913522	uncertain significance	Desmoid disease, hereditary; Familial adenomatous polyposis 1	2021-03-25	criteria provided, single submitter	clinical testing
ITMI	RCV000120050	SCV000084186	not provided	not specified	2013-09-19	no assertion provided	reference population
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000589545	SCV001799446	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000589545	SCV001922571	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004739410	SCV005362789	likely benign	APC-related disorder	2024-05-16	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).