Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076621 | SCV000107656 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Gene |
RCV000236121 | SCV000292617 | pathogenic | not provided | 2016-09-21 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted MSH2 c.508C>T at the cDNA level and p.Gln170Ter (Q170X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in multiple individuals with a personal and family history consistent with Lynch syndrome and is considered pathogenic (Mangold 2005, Irmejs 2007, Walsh 2010, Liu 2014). |
| Invitae | RCV000791416 | SCV000548130 | pathogenic | Hereditary nonpolyposis colon cancer | 2018-11-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln170*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This particular variant has been reported in the literature in individuals affected with Lynch syndrome or Lynch syndrome-associated cancers (PMID: 15849733, 17348456, 24710284, 20215533, 26485756). ClinVar contains an entry for this variant (Variation ID: 91117). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000491287 | SCV000580397 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-08-03 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense) |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000236121 | SCV000889443 | pathogenic | not provided | 2017-09-07 | criteria provided, single submitter | clinical testing | |
| German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne, |
RCV000785436 | SCV000924008 | pathogenic | Ovarian Neoplasms | 2018-12-01 | no assertion criteria provided | research |