ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.289C>T (p.Gln97Ter) (rs63750970)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076556 SCV000107585 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
GeneDx RCV000160586 SCV000211180 pathogenic not provided 2014-07-28 criteria provided, single submitter clinical testing This pathogenic variant is denoted MSH2 c.289C>T at the cDNA level and p.Gln97Ter (Q97X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in association with Lynch syndrome (Mangold 2004). We therefore consider this variant to be pathogenic.
Counsyl RCV000409729 SCV000489240 pathogenic Lynch syndrome I 2016-09-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491888 SCV000580464 pathogenic Hereditary cancer-predisposing syndrome 2018-07-10 criteria provided, single submitter clinical testing The p.Q97* pathogenic mutation (also known as c.289C>T), located in coding exon 2 of the MSH2 gene, results from a C to T substitution at nucleotide position 289. This changes the amino acid from a glutamine to a stop codon within coding exon 2. This pathogenic mutation has been reported in multiple individuals and/or families with Lynch syndrome (Mangold E et al. J. Med. Genet. 2004 Jul;41:567-72; Dominguez-Valentin M et al. Hered Cancer Clin Pract. 2013 Dec;11:18; Siraj AK et al. Cancer. 2015 Jun;121:1762-71; Rossi BM et al. BMC Cancer. 2017 Sep;17:623). The p.Q97* mutation was also identified in 1/10030 consecutive patients referred for evaluation by an NGS hereditary cancer panel, and that patient had a personal history of appendicle, throat, and colon cancers (Susswein LR et al. Genet. Med. 2016 08;18:823-32). 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.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000409729 SCV000781767 pathogenic Lynch syndrome I 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000699084 SCV000827779 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-03-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln97*) 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 individuals with colorectal cancer and clinical features of Lynch syndrome (PMID: 15235030, 26681312, 28874130, 24344984, 25712738). ClinVar contains an entry for this variant (Variation ID: 91054). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Color RCV000491888 SCV001348702 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000160586 SCV001450323 pathogenic not provided 2016-06-07 criteria provided, single submitter clinical testing

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