Submissions for variant NM_000038.6(APC):c.3342A>G (p.Arg1114=)

dbSNP: rs786201145

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000162762	SCV000213239	likely benign	Hereditary cancer-predisposing syndrome	2019-09-23	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV004019953	SCV000647442	likely benign	Familial adenomatous polyposis 1	2024-10-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000614189	SCV000722485	likely benign	not specified	2017-08-27	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.
Color Diagnostics, LLC DBA Color Health	RCV000162762	SCV001353118	likely benign	Hereditary cancer-predisposing syndrome	2019-02-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995215	SCV004839797	likely benign	Classic or attenuated familial adenomatous polyposis	2023-05-16	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004019953	SCV004933137	benign	Familial adenomatous polyposis 1	2024-03-18	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	RCV001355301	SCV001550151	uncertain significance	Endometrial carcinoma		no assertion criteria provided	clinical testing	The APC p.Arg1114= variant was not identified in the literature nor was it identified in the GeneInsight-COGR, Cosmic, MutDB, LOVD 3.0, UMD-LSDB, or Zhejiang University, databases. The variant was identified in dbSNP (ID: rs786201145) as "With Uncertain significance allele", and in ClinVar database (classified as likely benign by Ambry Genetics and GeneDx; as uncertain significance by Invitae). The variant was identified in control databases in 1 of 245228 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 1 of 110948 chromosomes (freq: 0.000009), while the variant was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Arg1114= 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. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.