Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076101 | SCV000107123 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Splicing aberration, >2 tumours with MSH2 immunoloss, co-segregation with disease & absent in 1000 genomes |
| Ambry Genetics | RCV000566772 | SCV000669873 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-07-19 | criteria provided, single submitter | clinical testing | The c.1277-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 8 in the MSH2 gene. This alteration has been reported in an individual with an MSI-high and MSH2 IHC absent colorectal cancer at age 33 (Overbeek LI et al. Br. J. Cancer, 2007 May;96:1605-12). This alteration has also been reported in two Norwegian families with an aggregation of colorectal cancers and was shown to give rise to aberrant splicing, specifically out of frame exon 8 skipping (Sjursen W et al. J. Med. Genet., 2010 Sep;47:579-85). This alteration has been classified as pathogenic using the following lines of evidence: in silico prediction models, segregation with disease, clinical phenotype including tumor characteristics, mutation co-occurrence, and functional studies (Thompson BA et al. Hum. Mutat. 2013 Jan;34:200-9; Thompson BA et al. Nat. Genet. 2014 Feb;46:107-15; available at [www.insight-group.org/variants/classifications/]). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. |
| Myriad Genetics, |
RCV003452820 | SCV004186617 | likely pathogenic | Lynch syndrome 1 | 2023-08-01 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
| Constitutional Genetics Lab, |
RCV001249916 | SCV001423933 | pathogenic | Lynch-like syndrome | 2019-07-01 | no assertion criteria provided | clinical testing | |
| Laboratory for Genotyping Development, |
RCV003162492 | SCV002758035 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |