ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1215C>A (p.Tyr405Ter)

dbSNP: rs63751271
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
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076063 SCV000107077 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing a premature termination codon
Ambry Genetics RCV002354267 SCV002659744 pathogenic Hereditary cancer-predisposing syndrome 2021-03-15 criteria provided, single submitter clinical testing The p.Y405* pathogenic mutation (also known as c.1215C>A), located in coding exon 7 of the MSH2 gene, results from a C to A substitution at nucleotide position 1215. This changes the amino acid from a tyrosine to a stop codon within coding exon 7. This alteration was reported in multiple Lynch syndrome families (Kurzawski G et al. Clin Genet, 2006 Jan;69:40-7; Dominguez-Valentin M et al. Hered Cancer Clin Pract, 2013 Dec;11:1; Jun SY et al. Oncotarget, 2017 Mar;8:21483-21500; Rossi BM et al. BMC Cancer, 2017 Sep;17:623; De Lellis L et al. PLoS One, 2013 Nov;8:e81194). 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.
Color Diagnostics, LLC DBA Color Health RCV002354267 SCV004356665 pathogenic Hereditary cancer-predisposing syndrome 2021-11-24 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 7 of the MSH2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with Lynch syndrome (PMID: 16451135, 20305446, 24278394, 31332305). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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.