ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1618del (p.Ser540fs)

dbSNP: rs1573553636
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
Ambry Genetics RCV001012435 SCV001172884 pathogenic Hereditary cancer-predisposing syndrome 2021-12-02 criteria provided, single submitter clinical testing The c.1618delA pathogenic mutation, located in coding exon 10 of the MSH2 gene, results from a deletion of one nucleotide at nucleotide position 1618, causing a translational frameshift with a predicted alternate stop codon (p.S540Vfs*3). This mutation has been detected in individuals with hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome, with at least one meeting Amsterdam criteria whose tumor demonstrated loss of MSH2 and MSH6 staining on immunohistochemistry (IHC) (Clarke EV et al. Fam Cancer, 2019 07;18:317-325; Ambry internal data). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV001384789 SCV001584436 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-06-22 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: 819674). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 30729418). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser540Valfs*3) in the MSH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816).
Myriad Genetics, Inc. RCV003455075 SCV004186824 pathogenic Lynch syndrome 1 2023-08-02 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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.