Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000202056 | SCV000149310 | pathogenic | not provided | 2018-06-20 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted MSH6 c.3142C>T at the cDNA level and p.Gln1048Ter (Q1048X) at the protein level. The substitution creates a nonsense variant, changing a Glutamine to a premature stop codon (CAG>TAG). This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one individual with colorectal cancer and one with endometrial cancer whose tumors showed loss of MSH6 via mismatch repair immunohistochemistry (Talseth-Palmer 2010, Buchanan 2014). Based on currently available evidence, we consider this variant to be pathogenic. |
Ambry Genetics | RCV000490956 | SCV000580150 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-10-11 | criteria provided, single submitter | clinical testing | Alterations resulting in premature truncation (e.g.reading frame shift, nonsense) |
Department of Pathology and Laboratory Medicine, |
RCV000500240 | SCV000592622 | pathogenic | Lynch syndrome | 2015-09-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000544323 | SCV000624821 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-11-09 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln1048*) 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 individuals affected with Lynch syndrome and colorectal and endometrial cancer (PMID: 20487569, 24323032, 27064304). ClinVar contains an entry for this variant (Variation ID: 127580). Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). For these reasons, this variant has been classified as Pathogenic. |
Mayo Clinic Genetic Testing Laboratories, |
RCV000202056 | SCV000257233 | pathogenic | not provided | no assertion criteria provided | research |