ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.589-17T>A

gnomAD frequency: 0.00001  dbSNP: rs754180618
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000679277 SCV000805977 uncertain significance not provided 2017-06-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001855627 SCV002316394 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-28 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the MLH1 gene. It does not directly change the encoded amino acid sequence of the MLH1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in the gain of 5 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is present in population databases (rs754180618, gnomAD 0.004%). This variant has been observed in individual(s) with colorectal cancer (PMID: 24802709). ClinVar contains an entry for this variant (Variation ID: 560784). Studies have shown that this variant results in the activation of a cryptic splice site in intron 7 (PMID: 24802709; Invitae). 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 RCV003163076 SCV003889619 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-18 criteria provided, single submitter clinical testing The c.589-17T>A intronic alteration consists of a T to A substitution 17 nucleotides before coding exon 8 in the MLH1 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV003465546 SCV004193057 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 2 2022-03-13 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.