Submissions for variant NM_000038.6(APC):c.4212C>T (p.Ser1404=)

dbSNP: rs144655979

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003766648	SCV000562666	likely benign	Familial adenomatous polyposis 1	2025-01-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000492038	SCV000579832	likely benign	Hereditary cancer-predisposing syndrome	2016-04-08	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.
Color Diagnostics, LLC DBA Color Health	RCV000492038	SCV000681657	likely benign	Hereditary cancer-predisposing syndrome	2017-05-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000732075	SCV000718252	likely benign	not provided	2018-05-29	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000732075	SCV000859977	uncertain significance	not provided	2018-03-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000615951	SCV001362430	likely benign	not specified	2020-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000732075	SCV004159223	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	APC: BP4, BP7
All of Us Research Program, National Institutes of Health	RCV004002226	SCV004837892	likely benign	Classic or attenuated familial adenomatous polyposis	2023-11-20	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003766648	SCV004931774	benign	Familial adenomatous polyposis 1	2024-03-26	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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000732075	SCV001549796	likely benign	not provided		no assertion criteria provided	clinical testing	The APC p.Ser1404Ser variant was not identified in the literature nor was it identified in the dbSNP, Genesight-COGR, Cosmic, MutDB, UMD-LSDB, Insight Colon Cancer Gene Variant Database, Zhejiang Colon Cancer Database, databases, but was identified in ClinVar (classified as likely benign by Invitae). The variant was not identified in the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project or the Exome Aggregation Consortium (August 8th 2016) control databases. The p.Ser1404Ser variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.