ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1597del (p.Cys533fs) (rs1559575107)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000690221 SCV000817900 pathogenic Hereditary nonpolyposis colorectal neoplasms 2018-04-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys533Valfs*2) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with suspected Lynch syndrome (PMID: 21642682). Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780424 SCV000917667 likely pathogenic Lynch syndrome 2018-12-21 criteria provided, single submitter clinical testing Variant summary: MLH1 c.1597delT (p.Cys533ValfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.1769T>G (p.Leu590X), c.1772_1775delATAG (p.Asp591fsX24), c.2084C>A (p.Ser695X)). The variant was absent in 246050 control chromosomes (gnomAD). c.1597delT has been reported in the literature in a family affected with Lynch Syndrome (Bonadona_2011). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Color Health, Inc RCV001186208 SCV001352559 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 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.