ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.588+1del

dbSNP: rs267607773
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075770 SCV000106778 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
Institute of Human Genetics, University of Leipzig Medical Center RCV001253171 SCV001428751 likely pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2019-11-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV002354264 SCV002652819 likely pathogenic Hereditary cancer-predisposing syndrome 2018-01-09 criteria provided, single submitter clinical testing The c.588+1delG intronic variant, located in intron 7 of the MLH1 gene, results from a deletion of one nucleotide within intron 7 of the MLH1 gene. This intronic variant has been reported in a German family suspected to have HNPCC/Lynch syndrome (Mangold E et al. Int. J. Cancer. 2005 Sep;116:692-702). Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, but is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. Using the Human Splicing Finder (HSF) splice site prediction tool, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable (Desmet FO et al. Nucleic Acids Res. 2009 May;37:e67). 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, Inc. RCV001253171 SCV005083691 likely pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2024-06-18 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.

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