Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075516 | SCV000106517 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Multifactorial likelihood analysis posterior probability >0.99 |
| Ambry Genetics | RCV002415536 | SCV002727787 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-02-13 | criteria provided, single submitter | clinical testing | The c.208-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 3 in the MLH1 gene. This variant has been reported in one Lynch syndrome family meeting Amsterdam I criteria (Tannergård P et al. Cancer Res., 1995 Dec;55:6092-6; Lagerstedt Robinson K et al. J. Natl. Cancer Inst., 2007 Feb;99:291-9). This variant has been identified in probands whose Lynch syndrome-associated tumors demonstrated loss of MLH1 and PMS2 expression by immunohistochemistry (Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Myriad Genetics, |
RCV003137610 | SCV003806604 | likely pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-01-11 | 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. |