Submissions for variant NM_000038.6(APC):c.2805C>G (p.Tyr935Ter)

dbSNP: rs137854575

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165582	SCV000216316	pathogenic	Hereditary cancer-predisposing syndrome	2021-08-23	criteria provided, single submitter	clinical testing	The p.Y935* pathogenic mutation (also known as c.2805C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 2805. This changes the amino acid from a tyrosine to a stop codon within coding exon 15. This mutation has been identified in numerous familial adenomatous polyposis (FAP) patients and families of various ethnicities to date (van der Luijt RB et al. Hum. Mutat. 1997;9:7-16; Kim DW et al. Hum. Mutat. 2005 Sep;26:281; Friedl W et al. Hered Cancer Clin Pract 2005 Sep;3:95-114; Kanter-Smoler G et al. BMC Med 2008 Apr;6:10; Mehenni H et al. Eur J Gastroenterol Hepatol, 2005 Dec;17:1407-12; Fodde R et al. Genomics, 1992 Aug;13:1162-8; Lagarde A et al. J. Med. Genet., 2010 Oct;47:721-2; Wallis YL et al. J. Med. Genet., 1999 Jan;36:14-20; Papp J et al. Fam. Cancer, 2016 Jan;15:85-97). 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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000500049	SCV000591119	pathogenic	Familial multiple polyposis syndrome	2015-12-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000202153	SCV000779345	pathogenic	not provided	2019-06-20	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; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 18554166, 16088911, 19822006, 17785554, 11933206, 16292097, 27978560, 16890597, 27705013, 8990002, 24233542, 24987355, 12007223, 28533537, 20223039, 26446593, 12173026, 16317745, 11748858, 15951963)
Labcorp Genetics (formerly Invitae), Labcorp	RCV004562359	SCV001372564	pathogenic	Familial adenomatous polyposis 1	2022-10-08	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 186058). This premature translational stop signal has been observed in individuals with familial adenomatous polyposis (PMID: 1324223, 1944466, 8381579, 8990002, 10083733, 10094547, 10713886, 11748858, 11933206, 12007223, 12173026, 15024739, 15108288, 16088911, 16317745, 17411426, 20685668, 20924072, 26300997; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr935*) in the APC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1909 amino acid(s) of the APC protein.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV003137694	SCV003807338	pathogenic	Gastric adenocarcinoma and proximal polyposis of the stomach	2022-11-25	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 strong, PS4 strong, PM2 moderated
Myriad Genetics, Inc.	RCV004562359	SCV004044858	pathogenic	Familial adenomatous polyposis 1	2023-05-05	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	RCV000202153	SCV000256956	pathogenic	not provided		no assertion criteria provided	research