Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000226342 | SCV000283730 | pathogenic | Lynch syndrome | 2017-01-04 | criteria provided, single submitter | clinical testing | This sequence change deletes 5 nucleotides and inserts 15 nucleotides in exon 4 of the MSH6 mRNA (c.2056_2060delinsCTTCTACCTCAAAAA), causing a frameshift at codon 686. This creates a premature translational stop signal (p.Gly686Leufs*15) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001328436 | SCV001519565 | likely pathogenic | Hereditary nonpolyposis colon cancer | 2021-03-16 | criteria provided, single submitter | clinical testing | Variant summary: MSH6 c.2056_2060delins15 (p.Gly686LeufsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (examples: c.2150_2153delTCAG p.Val717AlafsX18; c.2230dupG p.Glu744GlyfsX12). The variant was absent in 250560 control chromosomes. To our knowledge, no occurrence of c.2056_2060delins15 in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Revvity Omics, |
RCV001782720 | SCV002023523 | likely pathogenic | not provided | 2021-03-09 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV003454688 | SCV004188290 | pathogenic | Lynch syndrome 5 | 2023-08-16 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Invitae | RCV003765456 | SCV004647780 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly686Leufs*15) 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. For these reasons, this variant has been classified as Pathogenic. |