Submissions for variant NM_000038.6(APC):c.3497_3501del (p.Lys1165_Tyr1166insTer)

dbSNP: rs1554085053

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268049	SCV001446653	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003337298	SCV004044791	pathogenic	Familial adenomatous polyposis 1	2023-05-08	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001268049	SCV000591145	pathogenic	not provided		no assertion criteria provided	clinical testing	The APC p.Tyr1166X variant was not identified in the literature. The variant was identified in the InSiGHT Colon Cancer Gene Variant Database-LOVD (1x unclassified) and in the UMD-APC database (1x as causal). The variant was not identified in the dbSNP, Clinvitae database, COSMIC, Zhejiang Colon Cancer Database-LOVD, ClinVar database, and GeneInsight - COGR database. The variant was identified by our laboratory in 1 individuals with FAP. The c.3947_3501delATAAT variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1166 and leads to a premature stop codon at position 1166. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the APC gene are an established mechanism of disease in familial adenomatous polyposis and is the type of variant expected to cause the disorder. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic.