Submissions for variant NM_000038.6(APC):c.7201C>T (p.Leu2401=)

gnomAD frequency: 0.01134  dbSNP: rs2229994

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035082	SCV000058722	benign	not specified	2012-04-24	criteria provided, single submitter	clinical testing	Leu2401Leu in exon 15 of APC: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1.3% (92/7020) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS/; rs2229994).
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513347	SCV000153892	benign	Familial adenomatous polyposis 1	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000128900	SCV000172761	benign	Hereditary cancer-predisposing syndrome	2014-10-22	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Eurofins Ntd Llc (ga)	RCV000035082	SCV000226393	benign	not specified	2014-08-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000303809	SCV000452043	benign	APC-Associated Polyposis Disorders	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Color Diagnostics, LLC DBA Color Health	RCV000128900	SCV000537383	benign	Hereditary cancer-predisposing syndrome	2016-03-17	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000755461	SCV000602509	benign	not provided	2024-10-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035082	SCV000805462	benign	not specified	2016-12-16	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000755461	SCV001133362	benign	not provided	2019-05-07	criteria provided, single submitter	clinical testing
GeneDx	RCV000755461	SCV001828324	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000128900	SCV002527512	benign	Hereditary cancer-predisposing syndrome	2021-05-11	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000035082	SCV002550651	benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000128900	SCV002819193	benign	Hereditary cancer-predisposing syndrome	2022-09-27	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV002513347	SCV004017527	benign	Familial adenomatous polyposis 1	2023-07-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996182	SCV004843515	benign	Classic or attenuated familial adenomatous polyposis	2024-09-27	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV002513347	SCV005084435	benign	Familial adenomatous polyposis 1	2024-04-09	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.
CeGaT Center for Human Genetics Tuebingen	RCV000755461	SCV005330169	benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing	APC: BP4, BP7, BS1, BS2
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353597	SCV000591206	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The p.Leu2401Leu variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, and is listed in the dbSNP database as coming from a "clinical source" (ID#: rs2229994) with an average heterozygosity of 0.022+/-0.103, therefore increasing the likelihood of this variant to be benign. It has been identified in our laboratory in one among the 973 individuals who have undergone APC testing. Additionally, it has been identified twice in the literature, in 2/258 (0.007% frequency) proband chromosomes and 1/1052 (0.001 frequency) control chromosomes where it was classified as a polymorhism (Hadjisavvas_2006_16650078, Zhou_2004_15122587). In summary, based on the above information, the p.Leu2401Leu variant is classified as predicted benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000035082	SCV000691763	benign	not specified		no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000128900	SCV000693489	likely benign	Hereditary cancer-predisposing syndrome	2017-11-10	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000035082	SCV001797677	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000035082	SCV001807005	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035082	SCV001920369	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035082	SCV001954359	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000035082	SCV001965728	benign	not specified		no assertion criteria provided	clinical testing