Submissions for variant NM_000038.6(APC):c.8402G>A (p.Arg2801Gln)

gnomAD frequency: 0.00004  dbSNP: rs754363694

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235635	SCV000292749	uncertain significance	not provided	2023-11-07	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)
Labcorp Genetics (formerly Invitae), Labcorp	RCV002518425	SCV000552636	uncertain significance	Familial adenomatous polyposis 1	2024-10-31	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2801 of the APC protein (p.Arg2801Gln). This variant is present in population databases (rs754363694, gnomAD 0.02%). 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: 245699). 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.
Color Diagnostics, LLC DBA Color Health	RCV000581244	SCV000687175	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-27	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 2801 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 4/269104 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.
Ambry Genetics	RCV000581244	SCV001178836	likely benign	Hereditary cancer-predisposing syndrome	2023-04-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000235635	SCV001470671	uncertain significance	not provided	2020-02-12	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000581244	SCV002526980	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-30	criteria provided, single submitter	curation
Baylor Genetics	RCV002518425	SCV004200254	uncertain significance	Familial adenomatous polyposis 1	2024-01-11	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003998899	SCV004835807	uncertain significance	Classic or attenuated familial adenomatous polyposis	2024-02-05	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glutamine at codon 2801 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 4/269104 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.