Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076561 | SCV000107591 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
Ambry Genetics | RCV000569740 | SCV000662286 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-07-31 | criteria provided, single submitter | clinical testing | The p.E101* pathogenic mutation (also known as c.301G>T), located in coding exon 2 of the MSH2 gene, results from a G to T substitution at nucleotide position 301. This changes the amino acid from a glutamic acid to a stop codon within coding exon 2. This mutation has been reported in an individual diagnosed with an early-onset, MSI-H colorectal cancer demonstrating loss of MSH2 and MSH6 protein expression by IHC and whose family history includes duodenal and gastric cancers (Rahner N et al. Acta Oncol, 2007;46:763-9). 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. |
Invitae | RCV001389138 | SCV001590388 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2016-09-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal at codon 101 (p.Glu101*) of the MSH2 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic. This particular variant has been reported in the literature in an individual affected with early-onset colorectal cancer (PMID: 17653898). |
Myriad Genetics, |
RCV003452932 | SCV004186821 | pathogenic | Lynch syndrome 1 | 2023-07-26 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |