Submissions for variant NM_000038.6(APC):c.1658G>A (p.Trp553Ter)

dbSNP: rs863225318

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003229818	SCV000552454	pathogenic	Familial adenomatous polyposis 1	2023-06-05	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 217935). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 1338764). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp553*) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668).
Ambry Genetics	RCV000572094	SCV000675880	pathogenic	Hereditary cancer-predisposing syndrome	2016-02-04	criteria provided, single submitter	clinical testing	The p.W553* pathogenic mutation (also known as c.1658G>A), located in coding exon 13 of the APC gene, results from a G to A substitution at nucleotide position 1658. This changes the amino acid from a tryptophan to a stop codon within coding exon 13.This mutation has been reported in an individual with familial adenomatous polyposis (FAP) (Nagase et al. Hum Mutat. 1992;1(6):467-73). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000202102	SCV001133303	pathogenic	not provided	2019-03-15	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
GeneDx	RCV000202102	SCV002012953	pathogenic	not provided	2021-10-18	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported in an individual with familial adenomatous polyposis (Nagase 1992); Not observed at significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 1338764)
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003229818	SCV003927256	pathogenic	Familial adenomatous polyposis 1	2023-05-31	criteria provided, single submitter	clinical testing	A known pathogenic mutation was detected in the APC gene (c.l658G>A). This sequence change creates a premature translational stop signal (p.Trp553*) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial adenomatous polyposis (PMID: 1338764). ClinVar contains an entry for this variant (Variation ID: 217935). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV003229818	SCV004044853	pathogenic	Familial adenomatous polyposis 1	2023-05-02	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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000202102	SCV000256930	pathogenic	not provided		no assertion criteria provided	research