Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000074812 | SCV000108021 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon (also interrupts canonical acceptor splice site) |
| Ambry Genetics | RCV000567808 | SCV000669999 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-09-21 | criteria provided, single submitter | clinical testing | The c.3173-1_3173delGA variant spans the exon/intron boundary of coding exon 5 in the MSH6 gene. This variant results from the deletion of 2 nucleotides at positions c.3173-1 to c.3173. The nucleotide region encompassed by the deletion includes the canonical acceptor site, which is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Invitae | RCV000822708 | SCV000963522 | likely pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-10-23 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 89347). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 4 of the MSH6 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985841 | SCV001134423 | pathogenic | not provided | 2019-06-07 | criteria provided, single submitter | clinical testing | The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data. |
| Myriad Genetics, |
RCV003450960 | SCV004189316 | likely pathogenic | Lynch syndrome 5 | 2023-08-22 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |
| Baylor Genetics | RCV003460679 | SCV004198111 | likely pathogenic | Endometrial carcinoma | 2022-11-23 | criteria provided, single submitter | clinical testing |