Submissions for variant NM_000038.6(APC):c.1722A>G (p.Glu574=)

gnomAD frequency: 0.00001  dbSNP: rs786201277

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163224	SCV000213748	likely benign	Hereditary cancer-predisposing syndrome	2015-02-20	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.
Illumina Laboratory Services, Illumina	RCV000317916	SCV000451992	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000421864	SCV000527146	likely benign	not specified	2016-04-25	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002515127	SCV000562643	likely benign	Familial adenomatous polyposis 1	2024-08-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163224	SCV000911730	likely benign	Hereditary cancer-predisposing syndrome	2018-05-01	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995240	SCV004837436	likely benign	Classic or attenuated familial adenomatous polyposis	2024-01-11	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV002515127	SCV004931878	benign	Familial adenomatous polyposis 1	2024-03-06	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.