Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075641 | SCV000106648 | likely pathogenic | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Interrupts canonical donor splice site |
Gene |
RCV000478493 | SCV000568564 | pathogenic | not provided | 2017-08-17 | criteria provided, single submitter | clinical testing | This variant is denoted MLH1 c.307-1G>C or IVS3-1G>C and consists of a G>C nucleotide substitution at the -1 position of intron 3 of the MLH1 gene. This variant destroys a canonical splice acceptor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in an individual with colon cancer and a family history of colon cancer (Isidro 2003). Based on the current evidence, we consider this variant to be pathogenic. |
Ambry Genetics | RCV002319436 | SCV002608664 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-06-06 | criteria provided, single submitter | clinical testing | The c.307-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 4 of the MLH1 gene. This nucleotide position is highly conserved in available vertebrate species. This variant has been reported in one Portuguese Lynch syndrome family meeting Amsterdam I criteria (Isidro G et al. Hum. Mutat., 2003 Nov;22:419-20). Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. 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. |
Myriad Genetics, |
RCV003451131 | SCV004189363 | likely pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-13 | 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. |