ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1401del (p.Glu467fs) (rs1553365711)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558184 SCV000625260 pathogenic Hereditary nonpolyposis colon cancer 2017-07-15 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 9 of the MSH2 mRNA (c.1401delA), causing a frameshift at codon 467. This creates a premature translational stop signal (p.Glu467Aspfs*4) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000588665 SCV000696214 likely pathogenic Lynch syndrome 2017-05-08 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.1401delA (p.Glu467Aspfs) variant results in a premature termination codon, predicted to cause a truncated or absent MSH2 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 (e.g., c.1477C>T [p.Gln493X], c.1576delA [p.Thr526fs). One in silico tool predicts a damaging outcome for this variant. This variant is absent from the large control database ExAC (0/121130 control chromosomes). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic until the presence of the variant in patient populations is established.

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.