Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| International Society for Gastrointestinal Hereditary Tumours |
RCV000075681 | SCV000106684 | likely pathogenic | Lynch syndrome | 2019-06-21 | reviewed by expert panel | curation | Interrupts canonical donor splice site |
| Gene |
RCV001356725 | SCV001983877 | pathogenic | not provided | 2022-02-14 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Observed in patients with Lynch-related cancers consistent with pathogenic variants in this gene (Lee 2005, DeRycke 2017); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32906206, 25525159, 15996210, 18726168, 28944238) |
| Ambry Genetics | RCV002354259 | SCV002622779 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-02-04 | criteria provided, single submitter | clinical testing | The c.380+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 4 in the MLH1 gene. This variant was identified in an Indian patient with microsatellite stable rectal cancer diagnosed at 32 whose family meet Amsterdam criteria I (Lee SC et al. Clin. Genet. 2005 Aug;68:137-45). This variant was also identified in 1/1231 colorectal cancer cases and in 0/93 unaffected controls; the carrier of this alteration was diagnosed with colorectal cancer prior to age 50 (DeRycke MS et al. Mol Genet Genomic Med 2017 Sep;5:553-569). This nucleotide position is highly conserved in available vertebrate species. Based on two different splice site prediction tools, this alteration is expected to abolish the native splice donor site; however, experimental evidence is not currently available. 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, |
RCV003451141 | SCV004188365 | 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. |
| Baylor Genetics | RCV003451141 | SCV004193040 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2022-08-05 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001356725 | SCV001551969 | uncertain significance | not provided | no assertion criteria provided | clinical testing |