Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075539 | SCV000106539 | likely pathogenic | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Interrupts canonical donor splice site |
Invitae | RCV001314807 | SCV001505355 | likely pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2022-10-28 | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site is associated with altered splicing resulting in exon 19 skipping (PMID: 24362816). ClinVar contains an entry for this variant (Variation ID: 90054). Disruption of this splice site has been observed in individual(s) with colorectal or ovarian cancer (PMID: 8592341, 14635101, 15365995). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 18 of the MLH1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. |
Myriad Genetics, |
RCV003451105 | SCV004185827 | likely pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-25 | 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. |