Submissions for variant NM_000038.6(APC):c.4479G>A (p.Thr1493=)

gnomAD frequency: 0.59177  dbSNP: rs41115

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035071	SCV000058711	benign	not specified	2020-07-27	criteria provided, single submitter	clinical testing	The p.Thr1493Thr variant in APC is classified as benign because it has been identified in 82% (16364/19946) of East Asian chromosomes, including 6724 homozygotes, by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1.
Eurofins Ntd Llc (ga)	RCV000035071	SCV000109824	benign	not specified	2016-03-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162372	SCV000212682	benign	Hereditary cancer-predisposing syndrome	2014-10-31	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.
PreventionGenetics, part of Exact Sciences	RCV000035071	SCV000301595	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000383485	SCV000452013	benign	APC-Associated Polyposis Disorders	2018-01-12	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001636617	SCV000602515	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003315552	SCV000647520	benign	Familial adenomatous polyposis 1	2024-02-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162372	SCV000681669	benign	Hereditary cancer-predisposing syndrome	2016-03-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001636617	SCV001847829	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496525	SCV002808339	benign	Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach	2022-05-24	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315552	SCV004017438	benign	Familial adenomatous polyposis 1	2023-07-07	criteria provided, single submitter	clinical testing
Systems Biology Platform Zhejiang California International NanoSystems Institute	RCV000074234	SCV000105827	cancer	Familial colorectal cancer		no assertion criteria provided	not provided	Converted during submission to other.
Mayo Clinic Laboratories, Mayo Clinic	RCV000035071	SCV000256997	benign	not specified		no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353469	SCV000591174	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The c.4479G>A, p.Thr1493Thr 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 dbSNP (rs_id: rs41115) as a common polymorphism with a global minor allele frequency of 0.338. It has not been previously identified by our laboratory, but has been reported in the literature in 72/2142 (frequency of 0.033) proband chromosomes from individuals with familiar adenamatous polyposis, colorectal carcinoma, papillary thyroid carcinoma and sporadic ependymoma. It has also been identified in 54/2322 (frequency of 0.023) control chromosomes, increasing the likelihood that the variant has no clinical significance (Rocco_2006, Azzopardi_2008_18199528, Chao_2006_16569251, Curia_2012_21995949, Jasperson_2010_20420945, Kamory_2008_18369740, Onilude_2006_16843107, Schwab_2008_18026870, Subramaniam_2007_18024325, Teijeiro_2009_19095577). In summary, based on the above information, this variant is classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000035071	SCV001742783	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035071	SCV001922241	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035071	SCV001953579	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000035071	SCV001971880	benign	not specified		no assertion criteria provided	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000162372	SCV002050302	benign	Hereditary cancer-predisposing syndrome	2021-12-21	no assertion criteria provided	clinical testing