Submissions for variant NM_000038.6(APC):c.7079G>T (p.Gly2360Val)

gnomAD frequency: 0.00001  dbSNP: rs750960862

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000205327	SCV000260308	uncertain significance	Familial adenomatous polyposis 1	2023-11-24	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2360 of the APC protein (p.Gly2360Val). This variant is present in population databases (rs750960862, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 220060). 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 with a negative predictive value of 95%. 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.
Counsyl	RCV000205327	SCV000785643	uncertain significance	Familial adenomatous polyposis 1	2017-10-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001026011	SCV001188311	uncertain significance	Hereditary cancer-predisposing syndrome	2024-10-21	criteria provided, single submitter	clinical testing	The p.G2360V variant (also known as c.7079G>T), located in coding exon 15 of the APC gene, results from a G to T substitution at nucleotide position 7079. The glycine at codon 2360 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx	RCV002247631	SCV002520192	uncertain significance	not provided	2022-05-16	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18199528)
Myriad Genetics, Inc.	RCV000205327	SCV004019845	uncertain significance	Familial adenomatous polyposis 1	2023-02-15	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
All of Us Research Program, National Institutes of Health	RCV003997608	SCV004828600	uncertain significance	Classic or attenuated familial adenomatous polyposis	2023-09-18	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with valine at codon 2360 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 3/249484 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.