ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.142G>T (p.Glu48Ter) (rs63750615)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076158 SCV000107174 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000076158 SCV000592452 pathogenic Lynch syndrome 2016-02-10 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506167 SCV000604262 pathogenic not specified 2016-11-26 criteria provided, single submitter clinical testing
Invitae RCV000537461 SCV000625261 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-02-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu48*) in the MSH2 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 several families affected with Lynch syndrome (PMID: 19419416, 20587412, 22371642). ClinVar contains an entry for this variant (Variation ID: 90662). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000662482 SCV000784980 pathogenic Lynch syndrome I 2017-10-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011543 SCV001171876 pathogenic Hereditary cancer-predisposing syndrome 2018-01-31 criteria provided, single submitter clinical testing The p.E48* pathogenic mutation (also known as c.142G>T), located in coding exon 1 of the MSH2 gene, results from a G to T substitution at nucleotide position 142. This changes the amino acid from a glutamic acid to a stop codon within coding exon 1. This mutation has been identified in numerous Lynch syndrome families to date (Tang R et al. Clin. Genet., 2009 Apr;75:334-45; Berends MJ et al. Int. J. Cancer, 2001 May;92:398-403; Sjursen W et al. J. Med. Genet., 2010 Sep;47:579-85; Zahary MN et al. World J. Gastroenterol., 2012 Feb;18:814-20). 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.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000582377 SCV000691895 pathogenic not provided no assertion criteria provided 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.