Submissions for variant NM_000038.6(APC):c.5708A>G (p.Asn1903Ser)

gnomAD frequency: 0.00002  dbSNP: rs750404000

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003650531	SCV000282784	uncertain significance	Familial adenomatous polyposis 1	2024-01-10	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1903 of the APC protein (p.Asn1903Ser). This variant is present in population databases (rs750404000, 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: 236622). 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	RCV000229356	SCV000489046	uncertain significance	Familial adenomatous polyposis 1	2016-08-12	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000506645	SCV000600117	uncertain significance	not provided	2021-05-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000569562	SCV000667423	likely benign	Hereditary cancer-predisposing syndrome	2020-11-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Color Diagnostics, LLC DBA Color Health	RCV000569562	SCV000906781	likely benign	Hereditary cancer-predisposing syndrome	2016-09-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000506645	SCV003921739	uncertain significance	not provided	2022-10-27	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, 28157215)
Myriad Genetics, Inc.	RCV000229356	SCV004019889	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.