Submissions for variant NM_000038.6(APC):c.5918G>A (p.Ser1973Asn)

gnomAD frequency: 0.00001  dbSNP: rs4987109

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000218058	SCV000276201	uncertain significance	Hereditary cancer-predisposing syndrome	2022-04-16	criteria provided, single submitter	clinical testing	The p.S1973N variant (also known as c.5918G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 5918. The serine at codon 1973 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health	RCV000218058	SCV000904789	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-29	criteria provided, single submitter	clinical testing	This missense variant replaces serine with asparagine at codon 1973 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 not been identified 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.
Invitae	RCV002515656	SCV001399624	uncertain significance	Familial adenomatous polyposis 1	2023-09-25	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1973 of the APC protein (p.Ser1973Asn). This variant is not present in population databases (gnomAD no frequency). 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: 232146). 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. 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.
GeneDx	RCV001563151	SCV001786040	uncertain significance	not provided	2022-09-30	criteria provided, single submitter	clinical testing	Not observed 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)
Baylor Genetics	RCV002515656	SCV004190779	uncertain significance	Familial adenomatous polyposis 1	2023-09-13	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000218058	SCV004228160	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003488476	SCV004241357	uncertain significance	not specified	2023-12-20	criteria provided, single submitter	clinical testing