Submissions for variant NM_000038.6(APC):c.3391C>T (p.Gln1131Ter)

dbSNP: rs878853438

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000430422	SCV000517423	pathogenic	not provided	2015-06-05	criteria provided, single submitter	clinical testing	This pathogenic variant is denoted APC c.3391C>T at the cDNA level and p.Gln1131Ter (Q1131X) 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 protein truncation. This variant has been reported in association with Familial Adenomatous Polyposis (Wu 2001, Rivera 2011) and is considered pathogenic.The presence of
Ambry Genetics	RCV000491908	SCV000579935	pathogenic	Hereditary cancer-predisposing syndrome	2016-11-22	criteria provided, single submitter	clinical testing	The p.Q1131* pathogenic mutation (also known as c.3391C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 3391. This changes the amino acid from a glutamine to a stop codon within coding exon 15. This mutation has been reported in individuals with clinical diagnoses of familial adenomatous polyposis, including 1/136 Spanish individuals with classic disease (Wu G et al. Genet. Test. 2001;5:281-90; Rivera B et al. Ann. Oncol. 2011 Apr;22:903-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Invitae	RCV003335273	SCV002202309	pathogenic	Familial adenomatous polyposis 1	2022-08-03	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant is expected to disrupt the EB1 and HDLG binding sites, which mediate interactions with the cytoskeleton (PMID: 15311282, 17293347). While functional studies have not been performed to directly test the effect on APC protein function, this suggests that disruption of the C-terminal portion of the protein is functionally important. A different truncation (p.Tyr2645Lysfs*14) that lies downstream of this variant has been determined to be pathogenic (PMID: 9824584, 1316610, 27081525, 8381579, 22135120, Invitae). This suggests that deletion of this region of the APC protein is causative of disease. ClinVar contains an entry for this variant (Variation ID: 236590). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 11960572, 20924072). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1131*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1713 amino acid(s) of the APC protein.
Myriad Genetics, Inc.	RCV003335273	SCV004045172	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.