Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000601053 | SCV000713261 | pathogenic | Lynch syndrome | 2017-07-13 | criteria provided, single submitter | clinical testing | The p.Glu807X variant in MSH6 has not been previously reported in individuals wi th Lynch syndrome and or in large population studies. This nonsense variant lead s to a premature termination codon at position 807, which is predicted to lead t o a truncated or absent protein. Heterozygous loss of function of the MSH6 gene is an established disease mechanism in Lynch syndrome. In summary, this variant meets criteria to be classified as pathogenic for Lynch syndrome in an autosomal dominant manner based upon predicted impact on the protein and absence from con trols. |
| Invitae | RCV000688489 | SCV000816103 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2018-04-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). This sequence change creates a premature translational stop signal (p.Glu807*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the InSiGHT variant database (PMID: 24362816). |
| Myriad Genetics, |
RCV003316777 | SCV004019469 | pathogenic | Lynch syndrome 5 | 2023-02-07 | 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. |