ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1038+1G>C

dbSNP: rs267607816
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075082 SCV000106071 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Invitae RCV002514334 SCV003525052 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-10-25 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. Studies have shown that disruption of this splice site results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 89613). Disruption of this splice site has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 21642682, 23354634, 30521064). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 11 of the MLH1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product.
Myriad Genetics, Inc. RCV003450998 SCV004187046 likely pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-19 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.
Ding PR Lab, Sun Yat-sen University Cancer Center RCV001093692 SCV001250876 pathogenic Lynch syndrome 1 no assertion criteria provided clinical testing
Constitutional Genetics Lab, Leon Berard Cancer Center RCV001249908 SCV001423925 pathogenic Lynch-like syndrome 2019-07-01 no assertion criteria provided clinical testing

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