Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000478947 | SCV000569892 | uncertain significance | not provided | 2022-09-25 | criteria provided, single submitter | clinical testing | Not observed at significant frequency 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 a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 21901162, 22608206, 18199528) |
Invitae | RCV003470563 | SCV000768060 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1105 of the APC protein (p.Arg1105Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 420874). 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 | RCV001019909 | SCV001181323 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-06 | criteria provided, single submitter | clinical testing | The p.R1105W variant (also known as c.3313C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 3313. The arginine at codon 1105 is replaced by tryptophan, 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, |
RCV001019909 | SCV001342410 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-10 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with tryptophan at codon 1105 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 an individual affected with breast cancer (PMID: 30443844). This variant has been identified in 3/281780 chromosomes 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. |
Baylor Genetics | RCV003470563 | SCV004199521 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-09 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000478947 | SCV004222482 | uncertain significance | not provided | 2022-12-28 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.000011 (3/281780 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with breast cancer (PMID: 30443844 (2020)) and as a somatic finding in an individual with colorectal carcinoma (PMIDs: 21901162 (2011) and 22608206 (2012)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
Center for Genomic Medicine, |
RCV003493598 | SCV004243235 | likely benign | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing |