Submissions for variant NM_000038.6(APC):c.1343dup (p.Ala449fs)

dbSNP: rs1554080695

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clinical Genetics and Genomics, Karolinska University Hospital	RCV001269860	SCV001450171	pathogenic	not provided	2016-01-14	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001269860	SCV000591069	pathogenic	not provided		no assertion criteria provided	clinical testing	The p.Ala449Cysfs*11 variant was not identified in the literature nor was it identified in the dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, COSMIC, MutDB, ‚ÄúInSiGHT Colon Cancer Database‚Zhejiang Colon Cancer Database‚ the ClinVar database, Clinvitae, GeneInsight COGR, and UMD Colon Genes databases. The p.Ala449Cysfs*11 duplication variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 449 and leads to a premature stop codon 11 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 and this DNA finding is consistent with this individual‚Äôs clinical diagnosis of FAP. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as pathogenic.