Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076019 | SCV000107040 | likely pathogenic | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Interrupts canonical donor splice site |
| Ambry Genetics | RCV000491682 | SCV000580498 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-06-10 | criteria provided, single submitter | clinical testing | The c.1077-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 7 of the MSH2 gene. This alteration has been reported in an individual diagnosed with colon cancer at age 36 whose tumor showed microsatellite instability and absent MSH2 staining on IHC (Canard G et al. Ann. Surg. Oncol., 2012 Mar;19:809-16). 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. |
| Color Diagnostics, |
RCV000491682 | SCV000684902 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-04-01 | criteria provided, single submitter | clinical testing | This variant causes a G to C nucleotide substitution at the -1 position of intron 6 of the MSH2 gene. Splice site prediction tools suggest that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284005 | SCV001469548 | pathogenic | not provided | 2019-09-18 | criteria provided, single submitter | clinical testing | The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity. |
| Sema4, |
RCV000491682 | SCV002528806 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-02 | criteria provided, single submitter | curation | |
| Myriad Genetics, |
RCV003452800 | SCV004188124 | pathogenic | Lynch syndrome 1 | 2023-07-31 | criteria provided, single submitter | clinical testing | This variant is considered 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. This variant is strongly associated with more severe personal and family histories of cancer, typical for individuals with pathogenic variants in this gene [PMID: 27363726]. |
| Baylor Genetics | RCV003452800 | SCV004196910 | pathogenic | Lynch syndrome 1 | 2022-04-12 | criteria provided, single submitter | clinical testing |