Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000528164 | SCV000624938 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2017-09-03 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. While no functional studies have been performed to test the effects of this particular variant on MSH6 protein function or stability, it is expected to delete the C-terminal portion of the conserved MutS domain (PMID: 17531815, 24100870). This domain is necessary for the heterodimerization of MSH6 and MSH2 (PMID: 15952900, 16464007). Two similar MSH6 variants, c.3959_3962delCAAG, creating a frameshift at codon 1320 (p.Ala1320Glufs*6), and c.3984_3987dupGTCA, creating a frameshift at codon 1330 (p.Leu1330Valfs*12), have been reported as Ashkenazi Jewish founder mutations known to cause Lynch syndrome (PMID: 21155762). This variant has not been reported in the literature in individuals with MSH6-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the MSH6 gene (p.Cys1294Metfs*29). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 67 amino acids of the MSH6 protein. |
Myriad Genetics, |
RCV003449516 | SCV004185854 | pathogenic | Lynch syndrome 5 | 2023-08-28 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |