Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000612966 | SCV000731265 | pathogenic | Lynch syndrome | 2016-11-17 | criteria provided, single submitter | clinical testing | The p.Thr914fs variant in MSH6 has not been previously reported in individuals w ith Lynch syndrome and was absent from large population studies, though the abil ity of these studies to accurately detect indels may be limited. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 914 and leads to a premature termination codon 32 amino a cids downstream. This alteration is then predicted to lead to a truncated or abs ent protein. Heterozygous loss of function of function of the MSH6 gene is an es tablished disease mechanism in colorectal cancer. In summary, this variant meets criteria to be classified as pathogenic for Lynch syndrome in an autosomal domi nant manner based upon absence from controls and the predicted impact to the pro tein. |
Invitae | RCV000816242 | SCV000956741 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-06-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Thr914Ilefs*32) 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: 517156). For these reasons, this variant has been classified as Pathogenic. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002476369 | SCV002774363 | pathogenic | not provided | 2021-08-24 | criteria provided, single submitter | clinical testing | This frameshift variant causes the premature termination of MSH6 protein synthesis. In addition, it has been identified in an individual undergoing genetic testing (PMID: 31447099 (2019)). Based on the available information, this variant is classified as pathogenic. |
Myriad Genetics, |
RCV003451449 | SCV004187071 | pathogenic | Lynch syndrome 5 | 2023-08-18 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |