Submissions for variant NM_000038.6(APC):c.5108G>C (p.Gly1703Ala)

gnomAD frequency: 0.00001  dbSNP: rs587778042

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000562439	SCV000667619	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-13	criteria provided, single submitter	clinical testing	The p.G1703A variant (also known as c.5108G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 5108. The glycine at codon 1703 is replaced by alanine, an amino acid with similar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Counsyl	RCV000663189	SCV000786362	uncertain significance	Familial adenomatous polyposis 1	2018-04-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000663189	SCV000956001	uncertain significance	Familial adenomatous polyposis 1	2025-01-26	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1703 of the APC protein (p.Gly1703Ala). This variant is present in population databases (rs587778042, gnomAD 0.0009%). 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: 133532). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Mendelics	RCV000663189	SCV001136922	uncertain significance	Familial adenomatous polyposis 1	2019-05-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000562439	SCV001344293	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-21	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with alanine at codon 1703 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 1/249570 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.
GeneDx	RCV001582590	SCV001820993	uncertain significance	not provided	2023-05-19	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; Identified in healthy individuals undergoing whole genome sequencing (Bodian et al., 2014); This variant is associated with the following publications: (PMID: 28230015, 18199528, 24728327)
Sema4, Sema4	RCV000562439	SCV002535042	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-22	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000663189	SCV004018785	uncertain significance	Familial adenomatous polyposis 1	2023-02-21	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.
Baylor Genetics	RCV000663189	SCV004192215	uncertain significance	Familial adenomatous polyposis 1	2024-02-28	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003997333	SCV004838005	uncertain significance	Classic or attenuated familial adenomatous polyposis	2023-07-10	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with alanine at codon 1703 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 1/249570 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.
ITMI	RCV000120042	SCV000084175	not provided	not specified	2013-09-19	no assertion provided	reference population