Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000076245 | SCV000107264 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
Ambry Genetics | RCV000490897 | SCV000580582 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-06-26 | criteria provided, single submitter | clinical testing | The c.1687dupT pathogenic mutation, located in coding exon 11 of the MSH2 gene, results from a duplication of T at nucleotide position 1687, causing a translational frameshift with a predicted alternate stop codon (p.Y563Lfs*5). This mutation has been reported in an individual with a tubular adenoma that had high microsatellite instability (MSI-H) and a loss of MSH2 staining on immunohistochemistry (IHC) (Pino MS et al. J Mol Diagn. 2009 May;11(3):238-47). 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 | RCV000689274 | SCV000816916 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2018-08-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has been reported in an individual affected with Lynch syndrome (PMID: 19324997). This variant is also known as 1687insT in the literature. ClinVar contains an entry for this variant (Variation ID: 90748). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr563Leufs*5) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. |
Myriad Genetics, |
RCV003452851 | SCV004187923 | pathogenic | Lynch syndrome 1 | 2023-08-03 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |