Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076253 | SCV000107272 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
| Invitae | RCV001053224 | SCV001217474 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-02-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has been observed in an individual affected with Lynch syndrome (PMID: 15855432). ClinVar contains an entry for this variant (Variation ID: 90756). This sequence change creates a premature translational stop signal (p.Thr568Asnfs*4) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002408593 | SCV002715513 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-04-04 | criteria provided, single submitter | clinical testing | The c.1702dupA pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a duplication of A at nucleotide position 1702, causing a translational frameshift with a predicted alternate stop codon (p.T568Nfs*4). This variant has been reported in the germline of a female diagnosed with rectal cancer exhibiting loss of MSH2 and MSH6 proteins by immunohistochemistry and meeting Amsterdam II criteria (Piñol V et al. JAMA, 2005 Apr;293:1986-94; Pérez-Carbonell L et al. Gut, 2012 Jun;61:865-72). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |