Submissions for variant NM_000038.6(APC):c.7891T>G (p.Ser2631Ala)

dbSNP: rs1060503376

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003766603	SCV000552778	uncertain significance	Familial adenomatous polyposis 1	2019-11-28	criteria provided, single submitter	clinical testing	In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an APC-related disease. This sequence change replaces serine with alanine at codon 2631 of the APC protein (p.Ser2631Ala). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and alanine.
Color Diagnostics, LLC DBA Color Health	RCV001524343	SCV001734155	uncertain significance	Hereditary cancer-predisposing syndrome	2020-07-20	criteria provided, single submitter	clinical testing	This missense variant replaces serine with alanine at codon 2631 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 hereditary cancer 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.
GeneDx	RCV001755701	SCV002006864	uncertain significance	not provided	2020-07-15	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); 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
Ambry Genetics	RCV001524343	SCV002675603	uncertain significance	Hereditary cancer-predisposing syndrome	2022-05-16	criteria provided, single submitter	clinical testing	The p.S2631A variant (also known as c.7891T>G), located in coding exon 15 of the APC gene, results from a T to G substitution at nucleotide position 7891. The serine at codon 2631 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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.