Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001246763 | SCV001420145 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2019-10-02 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the MSH6 gene (p.Phe1323Argfs*3). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acids of the MSH6 protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the MSH6 protein. Other variant(s) that disrupt this region (p.Leu1330Valfs*12, p.Arg1334Ilefs*8) have been determined to be pathogenic (PMID: 19851887, 21155762, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with MSH6-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002375301 | SCV002624462 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-05-20 | criteria provided, single submitter | clinical testing | The c.3962_3965dupGAGA pathogenic mutation, located in coding exon 9 of the MSH6 gene, results from a duplication of GAGA at nucleotide position 3962, causing a translational frameshift with a predicted alternate stop codon (p.F1323Rfs*3). This alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. |
| Myriad Genetics, |
RCV003449790 | SCV004187388 | pathogenic | Lynch syndrome 5 | 2023-07-25 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |