Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003651879 | SCV000552694 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2751 of the APC protein (p.Thr2751Ala). 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: 411504). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587487 | SCV000694138 | uncertain significance | not provided | 2016-12-22 | criteria provided, single submitter | clinical testing | Variant summary: The APC c.8251A>G (p.Thr2751Ala) variant located in the EB-1 binding domain (via InterPro) causes a missense change involving a non-conserved nucleotide, which 3/4 in silico tools (SNPs&GO not captured here due to low reliability index) predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications and/or reputable clinical diagnostic laboratories/databases. Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)." |
Ambry Genetics | RCV001027324 | SCV001189864 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-03 | criteria provided, single submitter | clinical testing | The p.T2751A variant (also known as c.8251A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 8251. The threonine at codon 2751 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well 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, |
RCV001027324 | SCV001735048 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-14 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with alanine at codon 2751 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. |
Gene |
RCV000587487 | SCV001816623 | uncertain significance | not provided | 2021-03-25 | 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 |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000587487 | SCV004220647 | uncertain significance | not provided | 2023-07-12 | criteria provided, single submitter | clinical testing | To the best of our knowledge, this variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |