Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001043808 | SCV001207573 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-07-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser580*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 841555). For these reasons, this variant has been classified as Pathogenic. |
Myriad Genetics, |
RCV003455178 | SCV004188217 | pathogenic | Lynch syndrome 5 | 2023-08-15 | 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. |
Department of Pathology and Laboratory Medicine, |
RCV001356226 | SCV001551340 | pathogenic | not provided | no assertion criteria provided | clinical testing | The MSH6 p.Ser580* variant was not identified in the literature nor was it identified in the dbSNP, ClinVar, or UMD-LSDB databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). The p.Ser580* variant leads to a premature stop codon at position 580 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the MSH6 gene are an established mechanism of disease in Lynch syndrome and is the type of variant expected to cause the disorder. In addition, this variant was identified in our laboratory in a patient with an MSH6-deficient colorectal tumour. In summary, based on the above information, this variant meets our laboratory’s criteria to be classified as pathogenic. |