Submissions for variant NM_000038.6(APC):c.3567dup (p.Ser1190fs)

dbSNP: rs1554085117

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000500243	SCV000591148	pathogenic	Carcinoma of colon		no assertion criteria provided	clinical testing	The APC p.Ser1190IlefsX18 variant was not identified in the literature nor was it identified in the following databases: dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, HGMD, COSMIC, MutDB, “Mismatch Repair Genes Variant Database”, “MMR Gene Unclassified Variants Database”, InSiGHT Colon Cancer Gene Variant Database, “Zhejiang Colon Cancer Database”, the ClinVar database, GeneInsight VariantWire database and UMD. The p.Ser1190IlefsX18 duplication variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1190 and leads to a premature stop codon 18 codons downstream. 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.