ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1354G>T (p.Glu452Ter)

dbSNP: rs267607954
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076132 SCV000107147 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing premature termination codon
Ambry Genetics RCV000573345 SCV000676095 pathogenic Hereditary cancer-predisposing syndrome 2021-11-22 criteria provided, single submitter clinical testing The p.E452* variant (also known as c.1354G>T), located in coding exon 8 of the MSH2 gene, results from a G to T substitution at nucleotide position 1354. This changes the amino acid from a glutamic acid to a stop codon within coding exon 8. This alteration was detected in a patient with colon cancer at age 44, whose tumor demonstrated absent MSH2 protein staining on immunohistochemistry (IHC) (Julié C et al. Am. J. Gastroenterol., 2008 Nov;103:2825-35). 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 RCV000791561 SCV000930817 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-12-24 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: 90636). This premature translational stop signal has been observed in individual(s) with colon cancer (PMID: 18759827). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu452*) 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. RCV003452825 SCV004189614 pathogenic Lynch syndrome 1 2023-10-12 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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