Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076654 | SCV000107689 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Invitae | RCV001225117 | SCV001397353 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-06-06 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with Lynch syndrome (PMID: 12362047). ClinVar contains an entry for this variant (Variation ID: 91150). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Glu205*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002354271 | SCV002654448 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-11-12 | criteria provided, single submitter | clinical testing | The p.E205* pathogenic mutation (also known as c.613G>T), located in coding exon 3 of the MSH2 gene, results from a G to T substitution at nucleotide position 613. This changes the amino acid from a glutamic acid to a stop codon within coding exon 3. This mutation, designated "E205X," has been reported in a Polish kindred with HNPCC (Kurzawski G et al. J. Med. Genet., 2002 Oct;39:E65; Kurzawski G et al. Clin. Genet. 2006 Jan;69:40-7). 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. |