Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075246 | SCV000106242 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Multifactorial likelihood analysis posterior probability >0.99 |
Ambry Genetics | RCV002399432 | SCV002705588 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-14 | criteria provided, single submitter | clinical testing | The c.1558+1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide after coding exon 13 of the MLH1 gene. This variant has been reported in an individual with MSI-H small bowel cancer whose family met Amsterdam criteria (Viel A et al. Community Genet, 1998;1:229-36) and has been reported in several Lynch syndrome families to date Rossi BM et al. Ann Surg Oncol, 2002 Jul;9:555-61; Wagner A et al. Am J Hum Genet, 2003 May;72:1088-100; Pedroni M et al. Dis Markers, 2007;23:179-87; Bozzao C et al. Cancer, 2011 Sep;117:4325-35; Rossi BM et al. BMC Cancer, 2017 Sep;17:623). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. 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, |
RCV003315592 | SCV004017895 | likely pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-04-11 | 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. |
Gene |
RCV001804813 | SCV002054049 | not provided | Lynch syndrome 1 | no assertion provided | literature only |