ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.340G>T (p.Glu114Ter) (rs878853815)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001034685 SCV000284166 pathogenic Hereditary nonpolyposis colorectal neoplasms 2019-04-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu114*) 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 individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 237395). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000228392 SCV000919697 likely pathogenic Lynch syndrome 2018-03-30 criteria provided, single submitter clinical testing Variant summary: MSH2 c.340G>T (p.Glu114X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.387_388delTC, p.Gln130fsX2; c.528_529delTG, p.Cys176X; c.704_705delAA, p.Lys235fsX20). The variant was absent in 121212 control chromosomes (ExAC). To our knowledge, no occurrence of c.340G>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission for a clinical diagnostic laboratory (evaluation after 2014) and a reputable database cite the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as likely pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985808 SCV001134362 pathogenic not provided 2019-01-09 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Ambry Genetics RCV001020232 SCV001181685 pathogenic Hereditary cancer-predisposing syndrome 2018-07-30 criteria provided, single submitter clinical testing The p.E114* pathogenic mutation (also known as c.340G>T), located in coding exon 2 of the MSH2 gene, results from a G to T substitution at nucleotide position 340. This changes the amino acid from a glutamic acid to a stop codon within coding exon 2. 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.

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