ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1203dup (p.Gln402fs)

dbSNP: rs63750586
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076060 SCV000107074 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation introducing a premature termination codon
Invitae RCV000538916 SCV000625236 pathogenic Hereditary nonpolyposis colorectal neoplasms 2017-06-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). This variant has been reported in individuals affected with Lynch syndrome (PMID: 20591884, 17453009). ClinVar contains an entry for this variant (Variation ID: 90564). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln402Thrfs*15) in the MSH2 gene. It is expected to result in an absent or disrupted protein product.
Counsyl RCV000576682 SCV000677789 pathogenic Lynch syndrome 1 2016-12-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002345385 SCV002653710 pathogenic Hereditary cancer-predisposing syndrome 2022-05-26 criteria provided, single submitter clinical testing The c.1203dupA pathogenic mutation, located in coding exon 7 of the MSH2 gene, results from a duplication of A at nucleotide position 1203, causing a translational frameshift with a predicted alternate stop codon (p.Q402Tfs*15). This mutation has been reported in individuals with MSI-H early onset colorectal cancers demonstrating loss of MSH2 and MSH6 expression by IHC (Overbeek LI et al. Br. J. Cancer 2007 May;96:1605-12). This mutation has also been identified in Lynch syndrome patients with urothelial bladder cancer and endometrial cancer (van der Post RS et al. J. Med. Genet. 2010 Jul;47:464-70; Jóri B et al. Oncotarget 2015 Dec;6:41108-22). This alteration was one of two somatic MSH2 frameshift mutations identified in an MSI-H colon tumor with loss of MSH2 and MSH6 by IHC (Haraldsdottir S et al. Gastroenterology 2014 Dec;147:1308-1316.e1). Of note, this alteration is also designated as c.1203dup, p.Gln402fs, and p.Gln402Thrfs*15 in published literature. 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.
Myriad Genetics, Inc. RCV000576682 SCV004018420 pathogenic Lynch syndrome 1 2023-03-23 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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