Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000536613 | SCV000624790 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-08-17 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV002289716 | SCV002581533 | uncertain significance | Mismatch repair cancer syndrome 3 | 2022-05-03 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002438282 | SCV002749406 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-19 | criteria provided, single submitter | clinical testing | The p.T914I variant (also known as c.2741C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 2741. The threonine at codon 914 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. In addition, the CoDP in silico tool predicts this alteration to have a minor impact on molecular function, with a score of 0.004 (Terui H et al. J. Biomed. Sci. 2013 Apr;20:25). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478107 | SCV004221191 | uncertain significance | not provided | 2023-07-07 | criteria provided, single submitter | clinical testing | In a large-scale breast cancer association study, this variant was observed in an individual with breast cancer (see LOVD (http://databases.lovd.nl/shared/genes/MSH6) and PMID: 33471991 (2021)). The frequency of this variant in the general population, 0.000004 (1/250928 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 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. |
| All of Us Research Program, |
RCV004003682 | SCV004843165 | uncertain significance | Lynch syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing |