Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000074686 | SCV000107889 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon |
| Ambry Genetics | RCV000564199 | SCV000673959 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-10-17 | criteria provided, single submitter | clinical testing | The c.1784delT pathogenic mutation, located in coding exon 4 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 1784, causing a translational frameshift with a predicted alternate stop codon. This mutation has been reported in multiple individuals and families with Lynch syndrome; some of whom have tumor testing results showing high microsatellite instability and loss of the MSH6 protein via immunohistochemical staining and/or who meet Amsterdam II and/or revised Bethesda criteria (Wijnen J et al. Nat. Genet., 1999 Oct;23:142-4; van Lier MG et al. J. Pathol., 2012 Apr;226:764-74; Baglietto L et al. J. Natl. Cancer Inst., 2010 Feb;102:193-201; Ramsoekh D et al. Gut, 2008 Nov;57:1539-44). 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 | RCV001854275 | SCV002243235 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-10-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89223). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 22081473). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu595Tyrfs*15) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). |
| Myriad Genetics, |
RCV003450931 | SCV004185780 | pathogenic | Lynch syndrome 5 | 2023-08-15 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001682753 | SCV001974269 | pathogenic | not provided | no assertion criteria provided | clinical testing |