Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000076473 | SCV000107503 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation introducing premature termination codon |
| Labcorp Genetics |
RCV001388595 | SCV001589649 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-07-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu811*) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 8581513). ClinVar contains an entry for this variant (Variation ID: 90971). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298462 | SCV002598592 | pathogenic | Hereditary nonpolyposis colon cancer | 2024-10-11 | criteria provided, single submitter | clinical testing | Variant summary: MSH2 c.2432T>G (p.Leu811X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251338 control chromosomes (gnomAD). c.2432T>G has been reported in the literature in individuals affected with MSH2-related conditions (examples: Miyaki_1995, Lu_1996, Domingo_2004). These data indicate that the variant is very likely associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 15342696, 8581513, 8613431, 9240418). ClinVar contains an entry for this variant (Variation ID: 90971). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Myriad Genetics, |
RCV003452910 | SCV004187834 | pathogenic | Lynch syndrome 1 | 2023-08-08 | 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. |