Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000441289 | SCV000516574 | pathogenic | not provided | 2015-03-30 | criteria provided, single submitter | clinical testing | This pathogenic variant is denoted MSH6 c.856G>T at the cDNA level and p.Glu286Ter (E286X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic. |
| Ambry Genetics | RCV002411309 | SCV002676242 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-31 | criteria provided, single submitter | clinical testing | The p.E286* pathogenic mutation (also known as c.856G>T), located in coding exon 4 of the MSH6 gene, results from a G to T substitution at nucleotide position 856. This changes the amino acid from a glutamic acid to a stop codon within coding exon 4. 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. |
| Labcorp Genetics |
RCV002521554 | SCV003353680 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-05-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu286*) 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: 379469). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV003449054 | SCV004188238 | pathogenic | Lynch syndrome 5 | 2023-08-11 | 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. |
| Baylor Genetics | RCV003463828 | SCV004198143 | likely pathogenic | Endometrial carcinoma | 2022-07-02 | criteria provided, single submitter | clinical testing |