Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075468 | SCV000106466 | likely pathogenic | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Interrupts canonical donor splice site |
| Invitae | RCV001854294 | SCV002243668 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2021-04-15 | 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, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 15849733, 11748856, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 89986). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 17 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). |
| Constitutional Genetics Lab, |
RCV001250002 | SCV001423903 | pathogenic | Lynch-like syndrome | 2019-07-01 | no assertion criteria provided | clinical testing |