Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075257 | SCV000106255 | pathogenic | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Variant causes splicing aberration predicted to produce truncated protein: full inactivation of variant allele. |
Counsyl | RCV000410283 | SCV000489020 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2016-08-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001201368 | SCV000543598 | pathogenic | Hereditary nonpolyposis colorectal neoplasms | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 13 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). This variant is present in population databases (rs267607836, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with MLH1-related conditions (PMID: 12373605, 24278394). ClinVar contains an entry for this variant (Variation ID: 89783). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 12183410, 22949379). For these reasons, this variant has been classified as Pathogenic. |
Department of Pathology and Laboratory Medicine, |
RCV000075257 | SCV000592411 | pathogenic | Lynch syndrome | 2014-04-07 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000520869 | SCV000617552 | pathogenic | not provided | 2019-12-02 | criteria provided, single submitter | clinical testing | Canonical splice site variant demonstrated to result in exon skipping in a gene for which loss-of-function is a known mechanism of disease (Nakagawa 2002); Observed in several families meeting Amsterdam Criteria or Bethesda Guidelines for Lynch syndrome (Gille 2002, Nakagawa 2002, Svrcek 2010, Bonadona 2011, De Lellis 2013); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at a significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 25525159, 24278394, 15555211, 12373605, 21642682, 22949379, 20947886, 30720243, 12183410) |
Myriad Genetics, |
RCV000410283 | SCV004018177 | pathogenic | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-03-15 | criteria provided, single submitter | clinical testing | This variant is considered 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. This variant is strongly associated with more severe personal and family histories of cancer, typical for individuals with pathogenic variants in this gene [PMID: 25085752]. |