Submissions for variant NM_000038.6(APC):c.2608C>T (p.Pro870Ser)

gnomAD frequency: 0.00917  dbSNP: rs33974176

Total submissions: 26

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035068	SCV000058708	likely benign	not specified	2011-03-29	criteria provided, single submitter	clinical testing	Pro870Ser in exon 15 of APC: The Pro870Ser variant has been reported in the lite rature in two individuals with multiple sporadic colorectal adenomas and was abs ent from 1938 age, sex, and race-matched control chromosomes (Azzopardi 2008). T his variant has been reported in dbSNP with a frequency of about 2% (rs 33974176 ). Proline (Pro) at amino acid position 870 is not highly conserved in mammals o r lower species, with mouse carrying an alanine and both chicken and frog carryi ng a serine (this variant). Collectively this data suggests a more likely benign role for this variant.
Eurofins Ntd Llc (ga)	RCV000035068	SCV000109816	benign	not specified	2013-10-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000035068	SCV000167002	benign	not specified	2013-12-31	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000157720	SCV000212890	benign	Hereditary cancer-predisposing syndrome	2014-11-19	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204735	SCV000261825	benign	Familial adenomatous polyposis 1	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000400276	SCV000451999	likely benign	APC-Associated Polyposis Disorders	2018-02-16	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Counsyl	RCV000204735	SCV000488432	benign	Familial adenomatous polyposis 1	2016-03-28	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000034382	SCV000610978	likely benign	not provided	2017-05-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000157720	SCV000681539	benign	Hereditary cancer-predisposing syndrome	2015-03-19	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659276	SCV000781074	likely benign	Familial multiple polyposis syndrome	2016-11-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035068	SCV000805384	benign	not specified	2016-11-09	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034382	SCV000883403	benign	not provided	2017-08-20	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000157720	SCV002538560	benign	Hereditary cancer-predisposing syndrome	2020-07-31	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000035068	SCV002550603	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000204735	SCV004017683	benign	Familial adenomatous polyposis 1	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000034382	SCV004159219	benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	APC: BP4, BS1, BS2
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000157720	SCV004228003	benign	Hereditary cancer-predisposing syndrome	2023-11-06	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000204735	SCV004931005	benign	Familial adenomatous polyposis 1	2024-03-15	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.
Breakthrough Genomics, Breakthrough Genomics	RCV000034382	SCV005226869	likely benign	not provided		criteria provided, single submitter	not provided
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034382	SCV000043116	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
ITMI	RCV000035068	SCV000084154	not provided	not specified	2013-09-19	no assertion provided	reference population
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353782	SCV000591113	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The APC p.Pro870Ser variant was identified by Azzopardi (2008) in 2 of 1382 proband chromosomes from individuals with colorectal adenomas and was absent in the 1938 control chromosomes evaluated from this study. The variant was also identified in the HGMD and LOVD databases, and in dbSNP (ID: rs33974176) with an average heterozygosity of 0.024+/-0.106. This variant occurs at a frequency of greater than 1% in some populations of origin, including the 1000 Genomes Project (1.2%) and NHLBI Exome Sequencing Project (3.2% in African American alleles), and is therefore classified as a polymorphism. The p.Pro870 residue is not conserved across mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD) do not suggest a high likelihood of impact of the variant to the protein. In addition, our laboratory has identified this variant co-occurring with a pathogenic APC variant in a patient sample, further increasing the likelihood that the p.Pro870Ser variant does not have clinical significance. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
True Health Diagnostics	RCV000157720	SCV000787833	likely benign	Hereditary cancer-predisposing syndrome	2018-01-12	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000035068	SCV001800515	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000035068	SCV001808904	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000035068	SCV001964363	benign	not specified		no assertion criteria provided	clinical testing