ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.3643+5G>A

dbSNP: rs2139454564
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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 RCV001886531 SCV002150031 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-04-24 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the MLH3 gene. It does not directly change the encoded amino acid sequence of the MLH3 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1381029). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV004041211 SCV002617837 uncertain significance not specified 2024-02-08 criteria provided, single submitter clinical testing The c.3643+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 5 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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