Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076396 | SCV000107433 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Variant causes splicing aberration, >2 MSI-H, segregation with disease & AF 0.00. |
| Ambry Genetics | RCV002415566 | SCV002726064 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-12-16 | criteria provided, single submitter | clinical testing | The c.212-478T>G intronic pathogenic mutation results from a T to G substitution 478 nucleotides upstream from coding exon 2 in the MSH2 gene. This alteration has been detected in two families which met Amsterdam I/II criteria for Lynch syndrome with concordant tumor results demonstrating microsatellite instability and/or loss of MSH2 protein expression on immunohistochemistry (Palma L et al. Gynecol. Oncol., 2008 Dec;111:575-8; Clendenning M et al. Fam. Cancer, 2011 Jun;10:297-301). Based on results from splicing assays using minigenes and/or RT-PCR results from patient samples, this alteration was found to create a canonical splice donor site, which together with an existing predicted cryptic acceptor site, caused a 75 nucleotide in-frame pseudoexon inclusion. Furthermore, this inserted sequence contained a premature termination codon, which was predicted to result in a truncated protein of 94 amino acids (Clendenning M et al. Fam. Cancer, 2011 Jun;10:297-301; van der Klift HM et al. Mol Genet Genomic Med, 2015 Jul;3:327-45). Based on the available evidence, this alteration is interpreted as a disease-causing mutation. |