Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075515 | SCV000106513 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Coding sequence variation resulting in a stop codon or interrupts canonical acceptor splice site |
| Invitae | RCV001854296 | SCV002164982 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-04-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as 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: 90030). Disruption of this splice site has been observed in individuals with Lynch syndrome (PMID: 18389388, 18931482, 25892863, 27601186). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 2 of the MLH1 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 MLH1 are known to be pathogenic (PMID: 15713769, 24362816). |
| Myriad Genetics, |
RCV003451101 | SCV004189352 | likely pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-12 | 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. |