Submissions for variant NM_000038.6(APC):c.1779G>A (p.Trp593Ter)

dbSNP: rs1554083132

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneKor MSA	RCV000708599	SCV000821692	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-01	criteria provided, single submitter	clinical testing	This variant is a single amino acid change from Tryptophan to a premature translational stop signal at codon 593 of the APC protein. This is expected to result in an absent or disrupted protein product. Truncating variants In APC are known to be pathogenic. This variant has been described in the international literature in an individual undergoing panel testing for hereditary syndrome (PMID: 31159747). The mutation database ClinVar contains entries for this variant (Variation ID: 433627).
Labcorp Genetics (formerly Invitae), Labcorp	RCV004564234	SCV001215795	pathogenic	Familial adenomatous polyposis 1	2019-02-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant has been observed in an individual affected with familial adenomatous polyposis (PMID: 1338764). ClinVar contains an entry for this variant (Variation ID: 433627). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp593*) in the APC gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics	RCV000708599	SCV002714862	pathogenic	Hereditary cancer-predisposing syndrome	2020-06-11	criteria provided, single submitter	clinical testing	The p.W593* pathogenic mutation (also known as c.1779G>A), located in coding exon 14 of the APC gene, results from a G to A substitution at nucleotide position 1779. This changes the amino acid from a tryptophan to a stop codon within coding exon 14. This alteration was identified in 1/1164 unrelated German index patients with a clinical diagnosis of FAP or AFAP (Friedl W et al. Hered Cancer Clin Pract, 2005 Sep;3:95-114). This alteration was also detected in 1/150 FAP patients (Nagase H et al. Hum. Mutat., 1992;1:467-73). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV004564234	SCV004043494	pathogenic	Familial adenomatous polyposis 1	2023-05-03	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.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796209	SCV005416761	pathogenic	Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PS4_Supporting
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000504103	SCV000591090	uncertain significance	not provided		no assertion criteria provided	clinical testing