Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000550483 | SCV000624729 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-19 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000572538 | SCV000669937 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-14 | criteria provided, single submitter | clinical testing | The p.T716A variant (also known as c.2146A>G), located in coding exon 4 of the MSH6 gene, results from an A to G substitution at nucleotide position 2146. The threonine at codon 716 is replaced by alanine, an amino acid with similar properties. 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 poorly 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, |
RCV000572538 | SCV000906821 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-17 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001548306 | SCV001768193 | uncertain significance | not provided | 2021-12-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as germline pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25980754, 22949379, 17531815, 21120944) |
Sema4, |
RCV000572538 | SCV002535702 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-10 | criteria provided, single submitter | curation | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001548306 | SCV004221169 | uncertain significance | not provided | 2023-07-13 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in one individual with colon cancer from The Cancer Genome Atlas dataset (PMID: 29684080 (2018)) and another individual with T-cell acute lymphoblastic leukemia (PMID: 31721781 (2019)). The frequency of this variant in the general population, 0.000004 (1/250930 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. 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. |
All of Us Research Program, |
RCV004003671 | SCV004836029 | uncertain significance | Lynch syndrome | 2023-12-01 | criteria provided, single submitter | clinical testing |