ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.307-1G>C

dbSNP: rs267607736
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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) RCV000075641 SCV000106648 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Interrupts canonical donor splice site
GeneDx 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, Inc. 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.

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