Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076442 | SCV000107470 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
| Myriad Genetics, |
RCV003452900 | SCV004187016 | pathogenic | Lynch syndrome 1 | 2023-08-08 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Ambry Genetics | RCV004019110 | SCV005033552 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-03-15 | criteria provided, single submitter | clinical testing | The c.2240_2241delTA variant, located in coding exon 14 of the MSH2 gene, results from a deletion of two nucleotides at nucleotide positions 2240 to 2241, causing a translational frameshift with a predicted alternate stop codon (p.I747Rfs*2). This mutation has been reported in the family of a Danish patient who was diagnosed with an astrocytoma at age 42 as well as metachronous colorectal cancer (Therkildsen C et al. Eur J Neurol, 2015 Apr;22:717-24). This mutation was also detected in a Spanish colorectal cancer patient who was diagnosed at age 41 and whose tumor showed high microsatellite instability and loss of MSH2 and MSH6 immunohistochemical staining (Pérez-Cabornero L et al. Cancer Prev Res (Phila), 2011 Oct;4:1546-55). (Garre P et al. Nat Genet, 2010 Oct;42:817-8; author reply 818). (Caldés T et al. Am J Gastroenterol, 2000 Sep;95:2389-90). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |