Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076060 | SCV000107074 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing a premature termination codon |
Invitae | RCV000538916 | SCV000625236 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2017-06-28 | criteria provided, single submitter | clinical testing | 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 reported in individuals affected with Lynch syndrome (PMID: 20591884, 17453009). ClinVar contains an entry for this variant (Variation ID: 90564). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln402Thrfs*15) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. |
Counsyl | RCV000576682 | SCV000677789 | pathogenic | Lynch syndrome 1 | 2016-12-27 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002345385 | SCV002653710 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-05-26 | criteria provided, single submitter | clinical testing | The c.1203dupA pathogenic mutation, located in coding exon 7 of the MSH2 gene, results from a duplication of A at nucleotide position 1203, causing a translational frameshift with a predicted alternate stop codon (p.Q402Tfs*15). This mutation has been reported in individuals with MSI-H early onset colorectal cancers demonstrating loss of MSH2 and MSH6 expression by IHC (Overbeek LI et al. Br. J. Cancer 2007 May;96:1605-12). This mutation has also been identified in Lynch syndrome patients with urothelial bladder cancer and endometrial cancer (van der Post RS et al. J. Med. Genet. 2010 Jul;47:464-70; Jóri B et al. Oncotarget 2015 Dec;6:41108-22). This alteration was one of two somatic MSH2 frameshift mutations identified in an MSI-H colon tumor with loss of MSH2 and MSH6 by IHC (Haraldsdottir S et al. Gastroenterology 2014 Dec;147:1308-1316.e1). Of note, this alteration is also designated as c.1203dup, p.Gln402fs, and p.Gln402Thrfs*15 in published literature. In addition to the clinical data presented in the literature, 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. |
Myriad Genetics, |
RCV000576682 | SCV004018420 | pathogenic | Lynch syndrome 1 | 2023-03-23 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |