ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1902del (p.Asn635fs)

dbSNP: rs587778956
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
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075415 SCV000106411 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
GeneDx RCV000657384 SCV000779117 pathogenic not provided 2017-09-05 criteria provided, single submitter clinical testing This deletion of one nucleotide in MLH1 is denoted c.1902delG at the cDNA level and p.Asn635ThrfsX2 (N635TfsX2) at the protein level. The normal sequence, with the base that is deleted in brackets, is AAGG[delG]AACC. The deletion causes a frameshift which changes an Asparagine to a Threonine at codon 635, and creates a premature stop codon at position 2 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Myriad Genetics, Inc. RCV003451079 SCV004190064 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-24 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Invitae RCV003758686 SCV004485945 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-12-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89936). This premature translational stop signal has been observed in individual(s) with MLH1-related conditions (PMID: 31054147). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn635Thrfs*2) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816).

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.