Submissions for variant NM_000038.6(APC):c.4326T>A (p.Pro1442=) (rs67622085)

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001081086	SCV000153860	benign	Familial adenomatous polyposis 1	2020-12-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000131961	SCV000187018	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
PreventionGenetics,PreventionGenetics	RCV000254138	SCV000301594	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000361337	SCV000452010	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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001283362	SCV000602525	benign	none provided	2020-04-01	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000512763	SCV000609170	likely benign	not provided	2017-05-01	criteria provided, single submitter	clinical testing
Color Health, Inc	RCV000131961	SCV000681660	benign	Hereditary cancer-predisposing syndrome	2016-03-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000512763	SCV001897989	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV001353752	SCV000591167	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The Pro1442Pro variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, is listed in dbSNP (rs67622085) from a clinical source with an average heterozygosity and standard error of 0.018 +/- 0.093, and a global minor allele frequency (MAF) of 0.006 (1000 Genomes). It has not been previously identified by our laboratory among the 973 individuals who have undergone APC testing, but has been reported in the literature in 5/528 proband chromosomes (frequency 0.009) from individuals with colorectal cancer and sporadic ependymomas. It was found at higher frequencies in the 4/282 control chromosomes (frequency 0.014), increasing the likelihood that this is a benign variant (Onilude_2006_16843107, Worm_2004_15133491, Zhou_2004_15122587). In summary, based on the above information, the p.Pro1442ro variant is classified as benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000254138	SCV000691748	likely benign	not specified		no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000131961	SCV000693482	benign	Hereditary cancer-predisposing syndrome	2017-09-28	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000254138	SCV001799289	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000254138	SCV001809111	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics,Academic Medical Center	RCV000254138	SCV001922838	benign	not specified		no assertion criteria provided	clinical testing
Human Genetics - Radboudumc,Radboudumc	RCV000254138	SCV001960148	benign	not specified		no assertion criteria provided	clinical testing