Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000115078 | SCV000148987 | uncertain significance | not provided | 2018-02-26 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.3145T>C at the cDNA level, p.Trp1049Arg (W1049R) at the protein level, and results in the change of a Tryptophan to an Arginine (TGG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. APC Trp1049Arg was not observed in large population cohorts (Lek 2016). This variant is located within the beta-catenin binding domain (Azzopardi 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available information, it is unclear whether APC Trp1049Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV003467019 | SCV000647429 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1049 of the APC protein (p.Trp1049Arg). 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: 127285). 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. |
Ambry Genetics | RCV000569217 | SCV000667443 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-04 | criteria provided, single submitter | clinical testing | The p.W1049R variant (also known as c.3145T>C), located in coding exon 15 of the APC gene, results from a T to C substitution at nucleotide position 3145. The tryptophan at codon 1049 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000569217 | SCV001735613 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-23 | criteria provided, single submitter | clinical testing | This missense variant replaces tryptophan with arginine at codon 1049 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 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. |
Sema4, |
RCV000569217 | SCV002530049 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-19 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV003467019 | SCV004198801 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-15 | criteria provided, single submitter | clinical testing |