Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000074658 | SCV000107860 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Molecular Diagnostics Laboratory, |
RCV005251057 | SCV005901713 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-02-25 | criteria provided, single submitter | clinical testing | PVS1, PP4, PM2_Supporting c.1477G>T, located in exon 4 of the MSH6 gene, is expected to result in loss of function by premature protein truncation before codon 493, p.(Glu493*)(PVS1). It is not present in the population database gnomAD v2.1.1, non-cancer dataset (PM2_Supporting). No effect is predicted on splicing by computational tools. It has been identified in a patient affected with colorectal cancer and its tumour immunohistochemistry (IHC) revealed loss of MSH6 protein expression (internal data)(PP4). To our knowledge, functional studies have not been reported for this variant. In addition, the variant was reported as a pathogenic variant in the Insight database (2013/09/05:‘Coding sequence variation resulting in a stop codon’). Based on currently available information, the variant c.1477G>T is classified as a pathogenic variant according to ClinGen-MMR Guidelines version 3.1. |