Submissions for variant NM_000038.6(APC):c.667C>T (p.Gln223Ter) (rs1554074738)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine,Sinai Health System	RCV000502052	SCV000591046	pathogenic	Familial adenomatous polyposis		criteria provided, single submitter	clinical testing
GeneDx	RCV000657601	SCV000779342	pathogenic	not provided	2017-06-12	criteria provided, single submitter	clinical testing	This variant is denoted APC c.667C>T at the cDNA level and p.Gln223Ter (Q223X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with Familial Adenomatous Polyposis, as well as in an individual with a Lynch syndrome-associated cancer and/or polyps (Lagarde 2010, Yurgelun 2015). We consider this variant to be pathogenic.
Invitae	RCV000700265	SCV000829013	pathogenic	Familial adenomatous polyposis 1	2018-06-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln223*) in the APC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with familial adenomatous polyposis (PMID: 20685668). ClinVar contains an entry for this variant (Variation ID: 433610). Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). For these reasons, this variant has been classified as Pathogenic.