ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.4090+2T>C

dbSNP: rs1890375980
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001204244 SCV001375443 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2019-09-12 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 11 of the MLH3 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with MLH3-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MLH3 cause disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004033607 SCV004090289 uncertain significance not specified 2023-07-05 criteria provided, single submitter clinical testing The c.4090+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 10 in the MLH3 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.

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