Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000074908 | SCV000108118 | likely pathogenic | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Interrupts canonical donor splice site |
| Ambry Genetics | RCV002345376 | SCV002618934 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-09-22 | criteria provided, single submitter | clinical testing | The c.3647-6_3647-1delTAACAG intronic pathogenic mutation, located in intron 7 of the MSH6 gene, results from a deletion of 6 nucleotides within intron 7 of the MSH6 gene. This nucleotide region is well conserved in available vertebrate species. This mutation has been reported in multiple individuals having features of hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome with isolated loss of MSH6 by immunohistochemistry in their colorectal or uterine/endometrial tumors (Ambry internal data; Nilbert M et al. Fam. Cancer, 2009 Jun;8:75-83; Klarskov L et al. Am. J. Surg. Pathol., 2011 Sep;35:1391-9; Okkels H et al. Appl. Immunohistochem. Mol. Morphol., 2012 Oct;20:470-7). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor 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. |