Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076097 | SCV000107119 | likely pathogenic | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Interrupts canonical donor splice site |
| University of Washington Department of Laboratory Medicine, |
RCV000076097 | SCV000887352 | pathogenic | Lynch syndrome | 2018-05-01 | criteria provided, single submitter | clinical testing | MSH2 NM_000251.2:c.1277-1G>A has a 99.4% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 1.56 to 1, generated from evidence of seeing this as a somatic mutation in a tumor without loss of heterozygosity at the MSH2 locus. See Shirts et al 2018, PMID 29887214. |
| Ambry Genetics | RCV002371915 | SCV002688709 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-02 | criteria provided, single submitter | clinical testing | The c.1277-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 8 of the MSH2 gene. This alteration has been detected in individuals meeting either Amsterdam criteria or Bethesda guidelines for hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome and each had colorectal tumors displaying high microsatellite instability with loss of MSH2 protein staining on immunohistochemistry (Sheng JQ et al. Chin J Dig Dis, 2006;7:197-205; Goldberg Y et al. Fam. Cancer, 2008 Apr;7:309-17; Tian W et al. Int J Cancer. 2019 Sep 1;145(5):1290-1298). Using a Bayesian analysis that incorporates tumor mutation data, this variant was classified as pathogenic (Shirts BH et al. Am J Hum Genet. 2018 Jul 5;103(1):19-29.). 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, |
RCV003452817 | SCV004186762 | 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. |