Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Diagnostic Laboratory, |
RCV000202809 | SCV000257789 | uncertain significance | Familial multiple polyposis syndrome | 2015-07-10 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000590375 | SCV000292465 | uncertain significance | not provided | 2023-09-28 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with colon or breast cancer (Chubb et al., 2015; Yehia et al., 2018); This variant is associated with the following publications: (PMID: 25559809, 25801821, 32277576, 29684080) |
Invitae | RCV003534490 | SCV000552520 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2525 of the APC protein (p.Arg2525Cys). 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 missense change has been observed in individual(s) with biliary tract cancer and/or colorectal cancer (PMID: 25559809, 36243179). ClinVar contains an entry for this variant (Variation ID: 218507). 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000236933 | SCV000600153 | uncertain significance | not specified | 2017-06-27 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000573374 | SCV000667438 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-14 | criteria provided, single submitter | clinical testing | The p.R2525C variant (also known as c.7573C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 7573. The arginine at codon 2525 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in 1/626 early-onset familial colorectal cancer cases ascertained through a population-based registry in the United Kingdom (Chubb D et al. J Clin Oncol, 2015 Feb;33:426-32). In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet, 2018 04;14:e1007352). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be inconclusive by in silico analyses. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000573374 | SCV000681877 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 2525 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 performed for this variant. This variant has been observed in an individual affected with colorectal cancer (PMID: 25559809). This variant has been identified in 13/250824 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590375 | SCV000694120 | uncertain significance | not provided | 2016-12-22 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000236933 | SCV002760367 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000590375 | SCV003826844 | uncertain significance | not provided | 2022-09-19 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV002517343 | SCV004197642 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-26 | criteria provided, single submitter | clinical testing |