Submissions for variant NM_000038.6(APC):c.597G>A (p.Ala199=)

gnomAD frequency: 0.00001  dbSNP: rs587780601

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003650382	SCV000166045	benign	Familial adenomatous polyposis 1	2024-01-09	criteria provided, single submitter	clinical testing
Counsyl	RCV000122788	SCV000488184	likely benign	Familial adenomatous polyposis 1	2016-01-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000443147	SCV000515412	likely benign	not specified	2016-08-16	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	RCV000571364	SCV000667372	likely benign	Hereditary cancer-predisposing syndrome	2015-05-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV000571364	SCV000687056	likely benign	Hereditary cancer-predisposing syndrome	2017-10-06	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000122788	SCV004015992	likely benign	Familial adenomatous polyposis 1	2023-07-07	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000122788	SCV004018778	benign	Familial adenomatous polyposis 1	2023-02-21	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000443147	SCV004037786	benign	not specified	2023-08-31	criteria provided, single submitter	clinical testing	Variant summary: APC c.597G>A alters a conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.8e-05 in 250624 control chromosomes. The observed variant frequency is approximately 1.23 fold of the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.597G>A in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV003925217	SCV004744822	likely benign	APC-related condition	2019-05-29	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).