Submissions for variant NM_000038.6(APC):c.235A>G (p.Ser79Gly)

dbSNP: rs1001856924

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel	RCV002534077	SCV003836578	likely benign	Familial adenomatous polyposis 1	2023-02-18	reviewed by expert panel	curation	The c.235A>G variant in APC is a missense variant predicted to cause substitution of serine by glycine at amino acid 79 (p.Ser79Gly). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). APC is defined by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) as a gene for which primarily truncating variants are known to cause disease (BP1). This variant has been observed in 6 heterozygous individuals with no features of FAP, worth 3 healthy individual points (BS2_Supporting; Ambry Genetics Internal Data; Invitae Internal Data). In summary, this variant meets the criteria to be classified as Likely Benign for FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: BS2_supporting, BP1. (VCEP specifications version 1; date of approval: 12/12/2022).
Color Diagnostics, LLC DBA Color Health	RCV000773537	SCV000907231	uncertain significance	Hereditary cancer-predisposing syndrome	2019-01-15	criteria provided, single submitter	clinical testing
Invitae	RCV003653290	SCV001395656	uncertain significance	Familial adenomatous polyposis 1	2023-04-22	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function. ClinVar contains an entry for this variant (Variation ID: 628873). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 79 of the APC protein (p.Ser79Gly).
Ambry Genetics	RCV000773537	SCV002733663	uncertain significance	Hereditary cancer-predisposing syndrome	2021-06-22	criteria provided, single submitter	clinical testing	The p.S79G variant (also known as c.235A>G), located in coding exon 3 of the APC gene, results from an A to G substitution at nucleotide position 235. The serine at codon 79 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153833	SCV003843420	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing