Submissions for variant NM_000038.6(APC):c.5432C>T (p.Ser1811Leu)

dbSNP: rs1060503325

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000461055	SCV000552647	uncertain significance	Familial adenomatous polyposis 1	2023-07-28	criteria provided, single submitter	clinical testing	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. 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. ClinVar contains an entry for this variant (Variation ID: 411473). This missense change has been observed in individual(s) with familial adenomatous polyposis (PMID: 26163615). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1811 of the APC protein (p.Ser1811Leu).
Counsyl	RCV000461055	SCV000786610	uncertain significance	Familial adenomatous polyposis 1	2018-06-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000775725	SCV000910147	uncertain significance	Hereditary cancer-predisposing syndrome	2021-04-06	criteria provided, single submitter	clinical testing	This missense variant replaces serine with leucine at codon 1811 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with familial adenomatous polyposis (PMID: 26163615, 29901124). This variant has been identified in 1/249694 chromosomes in the general population by the Genome Aggregation Database (gnomAD) and in healthy control individuals (PMID: 32980694). 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	RCV000775725	SCV002652231	uncertain significance	Hereditary cancer-predisposing syndrome	2024-10-24	criteria provided, single submitter	clinical testing	The p.S1811L variant (also known as c.5432C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 5432. The serine at codon 1811 is replaced by leucine, an amino acid with dissimilar properties. This alteration was identified in a cohort of Chinese familial adenomatous polyposis (FAP) families (Chen QW et al. Asian Pac. J. Cancer Prev. 2015;16:4915-20). This amino acid position is not well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Myriad Genetics, Inc.	RCV000461055	SCV004018430	uncertain significance	Familial adenomatous polyposis 1	2023-02-14	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.